Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Neuronal circuitry for pain processing in the dorsal horn

Key Points

  • The spinal dorsal horn is innervated by primary afferent fibres and contains a large number of excitatory (glutamatergic) and inhibitory (GABA (γ-aminobutyric acid)-ergic or glycinergic) interneurons, as well as projection neurons that convey sensory information to several brain areas. The interneurons regulate transmission of this information to projection cells and to local reflex pathways. There are also descending modulatory inputs from the brainstem.

  • The dorsal horn can be divided into six parallel laminae, each of which has a distinctive pattern of primary afferent input — for example, nociceptive primary afferents terminate mainly in lamina I and lamina II. Projection neurons are concentrated in lamina I and scattered through laminae III–VI. In all laminae, interneurons make up the great majority of the neuronal population.

  • Despite its importance in pain mechanisms, we still know little about the neuronal organisation and synaptic circuitry of the dorsal horn. This is largely because of the diversity of the neurons, which has made it difficult to recognize functional populations.

  • Recent studies have begun to reveal discrete classes of inhibitory and excitatory interneurons, as well as certain distinctive types of projection neuron. There have also been important advances in our understanding of the structure and function of primary afferents.

  • Based on these studies, we can now begin to map some of the neuronal circuits. For example, many projection neurons in lamina I and some of those in lamina III receive a powerful direct input from nociceptive primary afferents. There is also evidence that projection neurons are selectively innervated by particular types of interneuron.

  • Several changes that could contribute to chronic pain have been identified in the dorsal horn following inflammation or nerve injury. Proposed mechanisms include changes affecting inhibitory interneurons or their synapses, development of long-term potentiation and alterations in the excitability of neurons.

  • Future studies will need to investigate the synaptic organization of the dorsal horn, and the expression of receptors and ion channels on different neuronal populations. These should lead to the identification of new molecular targets for pain treatment, as well as allowing us to identify (and ideally prevent) changes in the dorsal horn that underlie chronic pain.

Abstract

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Laminar organization of the dorsal horn and primary afferent inputs.
Figure 2: Classification of lamina II interneurons.
Figure 3: Projection neurons.
Figure 4: Neuronal circuits involving projection neurons.

Similar content being viewed by others

References

  1. Sivilotti, L. & Woolf, C. J. The contribution of GABAA and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord. J. Neurophysiol. 72, 169–179 (1994).

    CAS  PubMed  Google Scholar 

  2. Yaksh, T. L. Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists. Pain 37, 111–123 (1989).

    CAS  PubMed  Google Scholar 

  3. Rexed, B. The cytoarchitectonic organization of the spinal cord in the cat. J. Comp. Neurol. 96, 414–495 (1952).

    CAS  PubMed  Google Scholar 

  4. Woodbury, C. J., Ritter, A. M. & Koerber, H. R. On the problem of lamination in the superficial dorsal horn of mammals: a reappraisal of the substantia gelatinosa in postnatal life. J. Comp. Neurol. 417, 88–102 (2000).

    CAS  PubMed  Google Scholar 

  5. Dhaka, A., Earley, T. J., Watson, J. & Patapoutian, A. Visualizing cold spots: TRPM8-expressing sensory neurons and their projections. J. Neurosci. 28, 566–575 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Liu, Q. et al. Molecular genetic visualization of a rare subset of unmyelinated sensory neurons that may detect gentle touch. Nature Neurosci. 10, 946–948 (2007).

    CAS  PubMed  Google Scholar 

  7. Seal, R. P. et al. Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors. Nature 462, 651–655 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Lawson, S. N., Crepps, B. A. & Perl, E. R. Relationship of substance P to afferent characteristics of dorsal root ganglion neurones in guinea-pig. J. Physiol. 505, 177–191 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Snider, W. D. & McMahon, S. B. Tackling pain at the source: new ideas about nociceptors. Neuron 20, 629–632 (1998).

    CAS  PubMed  Google Scholar 

  10. Taylor, A. M., Peleshok, J. C. & Ribeiro-da-Silva, A. Distribution of P2X(3)-immunoreactive fibers in hairy and glabrous skin of the rat. J. Comp. Neurol. 514, 555–566 (2009).

    CAS  PubMed  Google Scholar 

  11. Bennett, D. L., Dmietrieva, N., Priestley, J. V., Clary, D. & McMahon, S. B. trkA, CGRP and IB4 expression in retrogradely labelled cutaneous and visceral primary sensory neurones in the rat. Neurosci. Lett. 206, 33–36 (1996).

    CAS  PubMed  Google Scholar 

  12. Perry, M. J. & Lawson, S. N. Differences in expression of oligosaccharides, neuropeptides, carbonic anhydrase and neurofilament in rat primary afferent neurons retrogradely labelled via skin, muscle or visceral nerves. Neuroscience 85, 293–310 (1998).

    CAS  PubMed  Google Scholar 

  13. Plenderleith, M. B. & Snow, P. J. The plant lectin Bandeiraea simplicifolia I-B4 identifies a subpopulation of small diameter primary sensory neurones which innervate the skin in the rat. Neurosci. Lett. 159, 17–20 (1993).

    CAS  PubMed  Google Scholar 

  14. Zylka, M. J., Rice, F. L. & Anderson, D. J. Topographically distinct epidermal nociceptive circuits revealed by axonal tracers targeted to Mrgprd. Neuron 45, 17–25 (2005).

    CAS  PubMed  Google Scholar 

  15. Cavanaugh, D. J. et al. Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli. Proc. Natl Acad. Sci. USA 106, 9075–9080 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Lynn, B. Effect of neonatal treatment with capsaicin on the numbers and properties of cutaneous afferent units from the hairy skin of the rat. Brain Res. 322, 255–260 (1984).

    CAS  PubMed  Google Scholar 

  17. Michael, G. J. et al. Nerve growth factor treatment increases brain-derived neurotrophic factor selectively in TrkA-expressing dorsal root ganglion cells and in their central terminations within the spinal cord. J. Neurosci. 17, 8476–8490 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Rethelyi, M., Light, A. R. & Perl, E. R. Synaptic complexes formed by functionally defined primary afferent units with fine myelinated fibers. J. Comp. Neurol. 207, 381–393 (1982).

    CAS  PubMed  Google Scholar 

  19. Ribeiro-da-Silva, A. & Coimbra, A. Two types of synaptic glomeruli and their distribution in laminae I-III of the rat spinal cord. J. Comp. Neurol. 209, 176–186 (1982).

    CAS  PubMed  Google Scholar 

  20. Ribeiro-da-Silva, A., Tagari, P. & Cuello, A. C. Morphological characterization of substance P-like immunoreactive glomeruli in the superficial dorsal horn of the rat spinal cord and trigeminal subnucleus caudalis: a quantitative study. J. Comp. Neurol. 281, 497–415 (1989).

    CAS  PubMed  Google Scholar 

  21. Zoli, M., Jansson, A., Sykova, E., Agnati, L. F. & Fuxe, K. Volume transmission in the CNS and its relevance for neuropsychopharmacology. Trends Pharmacol. Sci. 20, 142–150 (1999).

    CAS  PubMed  Google Scholar 

  22. Antal, M., Petko, M., Polgar, E., Heizmann, C. W. & Storm-Mathisen, J. Direct evidence of an extensive GABAergic innervation of the spinal dorsal horn by fibres descending from the rostral ventromedial medulla. Neuroscience 73, 509–518 (1996).

    CAS  PubMed  Google Scholar 

  23. Kato, G. et al. Direct GABAergic and glycinergic inhibition of the substantia gelatinosa from the rostral ventromedial medulla revealed by in vivo patch-clamp analysis in rats. J. Neurosci. 26, 1787–1794 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Polgár, E. et al. Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain. Pain 104, 229–239 (2003).

    PubMed  Google Scholar 

  25. Todd, A. J. & Sullivan, A. C. Light microscope study of the coexistence of GABA-like and glycine-like immunoreactivities in the spinal cord of the rat. J. Comp. Neurol. 296, 496–505 (1990).

    CAS  PubMed  Google Scholar 

  26. Keller, A. F., Coull, J. A., Chery, N., Poisbeau, P. & De Koninck, Y. Region-specific developmental specialization of GABA-glycine cosynapses in laminas I-II of the rat spinal dorsal horn. J. Neurosci. 21, 7871–7880 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Yasaka, T. et al. Cell-type-specific excitatory and inhibitory circuits involving primary afferents in the substantia gelatinosa of the rat spinal dorsal horn in vitro. J. Physiol. 581, 603–618 (2007).

    PubMed  PubMed Central  Google Scholar 

  28. Todd, A. J. et al. The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn. Eur. J. Neurosci. 17, 13–27 (2003).

    CAS  PubMed  Google Scholar 

  29. Maxwell, D. J., Belle, M. D., Cheunsuang, O., Stewart, A. & Morris, R. Morphology of inhibitory and excitatory interneurons in superficial laminae of the rat dorsal horn. J. Physiol. 584, 521–533 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Yasaka, T., Tiong, S. Y. X., Hughes, D. I., Riddell, J. S. & Todd, A. J. Populations of inhibitory and excitatory interneurons in lamina II of the adult rat spinal dorsal horn revealed by a combined electrophysiological and anatomical approach. Pain 151, 475–488 (2010). A recent study that compared physiological and morphological properties of lamina II interneurons with neurotransmitter phenotype and showed that A-type potassium current firing patterns were largely restricted to glutamatergic cells.

    PubMed  PubMed Central  Google Scholar 

  31. Graham, B. A., Brichta, A. M. & Callister, R. J. Moving from an averaged to specific view of spinal cord pain processing circuits. J. Neurophysiol. 98, 1057–1063 (2007). A review that highlights the heterogeneity of neurons in the superficial dorsal horn and emphasizes the need to identify functional populations.

    CAS  PubMed  Google Scholar 

  32. Ruscheweyh, R. & Sandkuhler, J. Lamina-specific membrane and discharge properties of rat spinal dorsal horn neurones in vitro. J. Physiol. 541, 231–244 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Hu, H. J. et al. The kv4.2 potassium channel subunit is required for pain plasticity. Neuron 50, 89–100 (2006). This study showed that Kv4.2, which is a downstream target for phosphorylation by extracellular signal-regulated kinases, mediates the majority of the A-type potassium currents in the dorsal horn and plays a crucial role in pain plasticity.

    CAS  PubMed  Google Scholar 

  34. Huang, H. Y. et al. Expression of A-type K channel α subunits Kv 4.2 and Kv 4.3 in rat spinal lamina II excitatory interneurons and colocalization with pain-modulating molecules. Eur. J. Neurosci. 22, 1149–1157 (2005).

    PubMed  Google Scholar 

  35. Grudt, T. J. & Perl, E. R. Correlations between neuronal morphology and electrophysiological features in the rodent superficial dorsal horn. J. Physiol. 540, 189–207 (2002). This combined physiological and morphological study developed the most widely used classification scheme for superficial dorsal horn neurons.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Hantman, A. W., van den Pol., A. N. & Perl, E. R. Morphological and physiological features of a set of spinal substantia gelatinosa neurons defined by green fluorescent protein expression. J. Neurosci. 24, 836–842 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Lu, Y. & Perl, E. R. A specific inhibitory pathway between substantia gelatinosa neurons receiving direct C-fiber input. J. Neurosci. 23, 8752–8758 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Lu, Y. & Perl, E. R. Modular organization of excitatory circuits between neurons of the spinal superficial dorsal horn (laminae I and II). J. Neurosci. 25, 3900–3907 (2005). One of a series of papers describing elegant studies in which paired recordings were used to investigate synaptic linkages in the superficial dorsal horn. In this case, a synaptic connection between glutamatergic vertical cells and NK1R-expressing lamina I projection neurons was revealed.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Todd, A. J. & McKenzie, J. GABA-immunoreactive neurons in the dorsal horn of the rat spinal cord. Neuroscience 31, 799–806 (1989).

    CAS  PubMed  Google Scholar 

  40. Albuquerque, C., Lee, C. J., Jackson, A. C. & MacDermott, A. B. Subpopulations of GABAergic and non-GABAergic rat dorsal horn neurons express Ca2+-permeable AMPA receptors. Eur. J. Neurosci. 11, 2758–2766 (1999).

    CAS  PubMed  Google Scholar 

  41. Zheng, J., Lu, Y. & Perl, E. R. Inhibitory neurones of the spinal substantia gelatinosa mediate interaction of signals from primary afferents. J. Physiol. 588, 2065–2075 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Hantman, A. W. & Perl, E. R. Molecular and genetic features of a labeled class of spinal substantia gelatinosa neurons in a transgenic mouse. J. Comp. Neurol. 492, 90–100 (2005).

    CAS  PubMed  Google Scholar 

  43. Han, Z. S., Zhang, E. T. & Craig, A. D. Nociceptive and thermoreceptive lamina I neurons are anatomically distinct. Nature Neurosci. 1, 218–225 (1998).

    CAS  PubMed  Google Scholar 

  44. Lima, D. & Coimbra, A. A Golgi study of the neuronal population of the marginal zone (lamina I) of the rat spinal cord. J. Comp. Neurol. 244, 53–71 (1986).

    CAS  PubMed  Google Scholar 

  45. Prescott, S. A. & De Koninck, Y. Four cell types with distinctive membrane properties and morphologies in lamina I of the spinal dorsal horn of the adult rat. J. Physiol. 539, 817–836 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Al Ghamdi, K. S., Polgar, E. & Todd, A. J. Soma size distinguishes projection neurons from neurokinin 1 receptor-expressing interneurons in lamina I of the rat lumbar spinal dorsal horn. Neuroscience 164, 1794–1804 (2009).

    CAS  PubMed  Google Scholar 

  47. Antal, M. et al. Different populations of parvalbumin- and calbindin-D28k-immunoreactive neurons contain GABA and accumulate 3H-D-aspartate in the dorsal horn of the rat spinal cord. J. Comp. Neurol. 314, 114–124 (1991).

    CAS  PubMed  Google Scholar 

  48. Todd, A. J. & Spike, R. C. The localization of classical transmitters and neuropeptides within neurons in laminae I–III of the mammalian spinal dorsal horn. Prog. Neurobiol. 41, 609–645 (1993).

    CAS  PubMed  Google Scholar 

  49. Polgár, E., Furuta, T., Kaneko, T. & Todd, A. Characterization of neurons that express preprotachykinin B in the dorsal horn of the rat spinal cord. Neuroscience 139, 687–697 (2006).

    PubMed  Google Scholar 

  50. Laing, I., Todd, A. J., Heizmann, C. W. & Schmidt, H. H. Subpopulations of GABAergic neurons in laminae I–III of rat spinal dorsal horn defined by coexistence with classical transmitters, peptides, nitric oxide synthase or parvalbumin. Neuroscience 61, 123–132 (1994).

    CAS  PubMed  Google Scholar 

  51. Mori, M., Kose, A., Tsujino, T. & Tanaka, C. Immunocytochemical localization of protein kinase C subspecies in the rat spinal cord: light and electron microscopic study. J. Comp. Neurol. 299, 167–177 (1990).

    CAS  PubMed  Google Scholar 

  52. Polgár, E., Fowler, J. H., McGill, M. M. & Todd, A. J. The types of neuron which contain protein kinase C gamma in rat spinal cord. Brain Res. 833, 71–80 (1999).

    PubMed  Google Scholar 

  53. Spike, R. C., Todd, A. J. & Johnston, H. M. Coexistence of NADPH diaphorase with GABA, glycine, and acetylcholine in rat spinal cord. J. Comp. Neurol. 335, 320–333 (1993).

    CAS  PubMed  Google Scholar 

  54. Burstein, R., Dado, R. J. & Giesler, G. J., Jr The cells of origin of the spinothalamic tract of the rat: a quantitative reexamination. Brain Res. 511, 329–337 (1990).

    CAS  PubMed  Google Scholar 

  55. Hylden, J. L., Anton, F. & Nahin, R. L. Spinal lamina I projection neurons in the rat: collateral innervation of parabrachial area and thalamus. Neuroscience 28, 27–37 (1989).

    CAS  PubMed  Google Scholar 

  56. Lima, D. & Coimbra, A. The spinothalamic system of the rat: structural types of retrogradely labelled neurons in the marginal zone (lamina I). Neuroscience 27, 215–230 (1988).

    CAS  PubMed  Google Scholar 

  57. Lima, D., Mendes-Ribeiro, J. A. & Coimbra, A. The spino-latero-reticular system of the rat: projections from the superficial dorsal horn and structural characterization of marginal neurons involved. Neuroscience 45, 137–152 (1991).

    CAS  PubMed  Google Scholar 

  58. Spike, R. C., Puskar, Z., Andrew, D. & Todd, A. J. A quantitative and morphological study of projection neurons in lamina I of the rat lumbar spinal cord. Eur. J. Neurosci. 18, 2433–2448 (2003).

    CAS  PubMed  Google Scholar 

  59. Todd, A. J., McGill, M. M. & Shehab, S. A. Neurokinin 1 receptor expression by neurons in laminae, I., III and IV of the rat spinal dorsal horn that project to the brainstem. Eur. J. Neurosci. 12, 689–700 (2000).

    CAS  PubMed  Google Scholar 

  60. Almarestani, L., Waters, S. M., Krause, J. E., Bennett, G. J. & Ribeiro-da-Silva, A. Morphological characterization of spinal cord dorsal horn lamina I neurons projecting to the parabrachial nucleus in the rat. J. Comp. Neurol. 504, 287–297 (2007).

    CAS  PubMed  Google Scholar 

  61. Bernard, J. F., Dallel, R., Raboisson, P., Villanueva, L. & Le Bars, D. Organization of the efferent projections from the spinal cervical enlargement to the parabrachial area and periaqueductal gray: a PHA-L study in the rat. J. Comp. Neurol. 353, 480–505 (1995).

    CAS  PubMed  Google Scholar 

  62. Feil, K. & Herbert, H. Topographic organization of spinal and trigeminal somatosensory pathways to the rat parabrachial and Kolliker-Fuse nuclei. J. Comp. Neurol. 353, 506–528 (1995).

    CAS  PubMed  Google Scholar 

  63. Gauriau, C. & Bernard, J. F. A comparative reappraisal of projections from the superficial laminae of the dorsal horn in the rat: the forebrain. J. Comp. Neurol. 468, 24–56 (2004).

    PubMed  Google Scholar 

  64. Slugg, R. M. & Light, A. R. Spinal cord and trigeminal projections to the pontine parabrachial region in the rat as demonstrated with Phaseolus vulgaris leucoagglutinin. J. Comp. Neurol. 339, 49–61 (1994).

    CAS  PubMed  Google Scholar 

  65. Al-Khater, K. M. & Todd, A. J. Collateral projections of neurons in laminae, I., III, and IV of rat spinal cord to thalamus, periaqueductal gray matter, and lateral parabrachial area. J. Comp. Neurol. 515, 629–646 (2009).

    PubMed  PubMed Central  Google Scholar 

  66. Al-Khater, K. M., Kerr, R. & Todd, A. J. A quantitative study of spinothalamic neurons in laminae, I, III, and IV in lumbar and cervical segments of the rat spinal cord. J. Comp. Neurol. 511, 1–18 (2008).

    PubMed  PubMed Central  Google Scholar 

  67. Polgár, E., Wright, L. L. & Todd, A. J. A quantitative study of brainstem projections from lamina I neurons in the cervical and lumbar enlargement of the rat. Brain Res. 1308, 58–67 (2010).

    PubMed  PubMed Central  Google Scholar 

  68. Zhang, E. T. & Craig, A. D. Morphology and distribution of spinothalamic lamina I neurons in the monkey. J. Neurosci. 17, 3274–3284 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Zhang, E. T., Han, Z. S. & Craig, A. D. Morphological classes of spinothalamic lamina I neurons in the cat. J. Comp. Neurol. 367, 537–549 (1996).

    CAS  PubMed  Google Scholar 

  70. Andrew, D. Sensitization of lamina I spinoparabrachial neurons parallels heat hyperalgesia in the chronic constriction injury model of neuropathic pain. J. Physiol. 587, 2005–2017 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Bester, H., Chapman, V., Besson, J. M. & Bernard, J. F. Physiological properties of the lamina I spinoparabrachial neurons in the rat. J. Neurophysiol. 83, 2239–2259 (2000).

    CAS  PubMed  Google Scholar 

  72. Ruscheweyh, R., Ikeda, H., Heinke, B. & Sandkuhler, J. Distinctive membrane and discharge properties of rat spinal lamina I projection neurones in vitro. J. Physiol. 555, 527–543 (2004).

    CAS  PubMed  Google Scholar 

  73. Zhang, X. & Giesler, G. J. Jr. Response characterstics of spinothalamic tract neurons that project to the posterior thalamus in rats. J. Neurophysiol. 93, 2552–2564 (2005).

    PubMed  Google Scholar 

  74. Willis, W. D., Trevino, D. L., Coulter, J. D. & Maunz, R. A. Responses of primate spinothalamic tract neurons to natural stimulation of hindlimb. J. Neurophysiol. 37, 358–372 (1974).

    CAS  PubMed  Google Scholar 

  75. Salter, M. W. & Henry, J. L. Responses of functionally identified neurones in the dorsal horn of the cat spinal cord to substance P, neurokinin A and physalaemin. Neuroscience 43, 601–610 (1991).

    CAS  PubMed  Google Scholar 

  76. Mantyh, P. W. et al. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278, 275–279 (1997). By selectively ablating NK1R-expressing dorsal horn neurons in vivo , the authors demonstrated that these cells play a pivotal part in the development of hyperalgesia.

    CAS  PubMed  Google Scholar 

  77. Nichols, M. L. et al. Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science 286, 1558–1561 (1999).

    CAS  PubMed  Google Scholar 

  78. Littlewood, N. K., Todd, A. J., Spike, R. C., Watt, C. & Shehab, S. A. The types of neuron in spinal dorsal horn which possess neurokinin-1 receptors. Neuroscience 66, 597–608 (1995).

    CAS  PubMed  Google Scholar 

  79. Yu, X. H. et al. NK-1 receptor immunoreactivity in distinct morphological types of lamina I neurons of the primate spinal cord. J. Neurosci. 19, 3545–3555 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Todd, A. J. et al. Projection neurons in lamina I of rat spinal cord with the neurokinin 1 receptor are selectively innervated by substance P-containing afferents and respond to noxious stimulation. J. Neurosci. 22, 4103–4113 (2002). This article demonstrated a strong monosynaptic input from substance P-containing (nociceptive) primary afferents to lamina I projection neurons that express the NK1R.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Polgár, E., Al Ghamdi, K. S. & Todd, A. J. Two populations of neurokinin 1 receptor-expressing projection neurons in lamina I of the rat spinal cord that differ in AMPA receptor subunit composition and density of excitatory synaptic input. Neuroscience 167, 1192–1204 (2010). This recent report identifies two populations of NK1R-expressing lamina I projection neurons that differ in their AMPAR subunit expression and in the density of excitatory synapses that they receive. It also provides evidence that GluA-containing receptors in the superficial dorsal horn are largely restricted to projection neurons.

    PubMed  Google Scholar 

  82. Polgár, E., Al-Khater, K. M., Shehab, S., Watanabe, M. & Todd, A. J. Large projection neurons in lamina I of the rat spinal cord that lack the neurokinin 1 receptor are densely innervated by VGLUT2-containing axons and possess GluR4-containing AMPA receptors. J. Neurosci. 28, 13150–13160 (2008).

    PubMed  PubMed Central  Google Scholar 

  83. Puskár, Z., Polgár, E. & Todd, A. J. A population of large lamina I projection neurons with selective inhibitory input in rat spinal cord. Neuroscience 102, 167–176 (2001).

    PubMed  Google Scholar 

  84. Naim, M., Spike, R. C., Watt, C., Shehab, S. A. & Todd, A. J. Cells in laminae III and IV of the rat spinal cord that possess the neurokinin-1 receptor and have dorsally directed dendrites receive a major synaptic input from tachykinin-containing primary afferents. J. Neurosci. 17, 5536–5548 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Polgár, E., Campbell, A. D., MacIntyre, L. M., Watanabe, M. & Todd, A. J. Phosphorylation of ERK in neurokinin 1 receptor-expressing neurons in laminae III and IV of the rat spinal dorsal horn following noxious stimulation. Mol. Pain 3, 4 (2007).

    PubMed  PubMed Central  Google Scholar 

  86. Naim, M. M., Shehab, S. A. & Todd, A. J. Cells in laminae III and IV of the rat spinal cord which possess the neurokinin-1 receptor receive monosynaptic input from myelinated primary afferents. Eur. J. Neurosci. 10, 3012–3019 (1998).

    CAS  PubMed  Google Scholar 

  87. Sakamoto, H., Spike, R. C. & Todd, A. J. Neurons in laminae III and IV of the rat spinal cord with the neurokinin-1 receptor receive few contacts from unmyelinated primary afferents which do not contain substance P. Neuroscience 94, 903–908 (1999).

    CAS  PubMed  Google Scholar 

  88. Polgár, E., Shehab, S. A., Watt, C. & Todd, A. J. GABAergic neurons that contain neuropeptide Y selectively target cells with the neurokinin 1 receptor in laminae III and IV of the rat spinal cord. J. Neurosci. 19, 2637–2646 (1999).

    PubMed  PubMed Central  Google Scholar 

  89. Uta, D. et al. TRPA1-expressing primary afferents synapse with a morphologically identified subclass of substantia gelatinosa neurons in the adult rat spinal cord. Eur. J. Neurosci. 31, 1960–1973 (2010).

    PubMed  PubMed Central  Google Scholar 

  90. Neumann, S., Braz, J. M., Skinner, K., Llewellyn-Smith, I. J. & Basbaum, A. I. Innocuous, not noxious, input activates PKCγ interneurons of the spinal dorsal horn via myelinated afferent fibers. J. Neurosci. 28, 7936–7944 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Hughes, D. I., Scott, D. T., Todd, A. J. & Riddell, J. S. Lack of evidence for sprouting of Abeta afferents into the superficial laminas of the spinal cord dorsal horn after nerve section. J. Neurosci. 23, 9491–9499 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Santos, S. F., Rebelo, S., Derkach, V. A. & Safronov, B. V. Excitatory interneurons dominate sensory processing in the spinal substantia gelatinosa of rat. J. Physiol. 581, 241–254 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Hughes, D. I. et al. P boutons in lamina IX of the rodent spinal cord express high levels of glutamic acid decarboxylase-65 and originate from cells in deep medial dorsal horn. Proc. Natl Acad. Sci. USA 102, 9038–9043 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Todd, A. J. GABA and glycine in synaptic glomeruli of the rat spinal dorsal horn. Eur. J. Neurosci. 8, 2492–2498 (1996).

    CAS  PubMed  Google Scholar 

  95. Watson, A. H., Hughes, D. I. & Bazzaz, A. A. Synaptic relationships between hair follicle afferents and neurones expressing GABA and glycine-like immunoreactivity in the spinal cord of the rat. J. Comp. Neurol. 452, 367–380 (2002).

    CAS  PubMed  Google Scholar 

  96. Mantyh, P. W. et al. Receptor endocytosis and dendrite reshaping in spinal neurons after somatosensory stimulation. Science 268, 1629–1632 (1995).

    CAS  PubMed  Google Scholar 

  97. Ding, Y. Q. et al. Two major distinct subpopulations of neurokinin-3 receptor-expressing neurons in the superficial dorsal horn of the rat spinal cord. Eur. J. Neurosci. 16, 551–556 (2002).

    PubMed  Google Scholar 

  98. Seybold, V. S. et al. Relationship of NK3 receptor-immunoreactivity to subpopulations of neurons in rat spinal cord. J. Comp. Neurol. 381, 439–448 (1997).

    CAS  PubMed  Google Scholar 

  99. Todd, A. J., Spike, R. C. & Polgar, E. A quantitative study of neurons which express neurokinin-1 or somatostatin sst2a receptor in rat spinal dorsal horn. Neuroscience 85, 459–473 (1998).

    CAS  PubMed  Google Scholar 

  100. Kemp, T., Spike, R. C., Watt, C. & Todd, A. J. The mu-opioid receptor (MOR1) is mainly restricted to neurons that do not contain GABA or glycine in the superficial dorsal horn of the rat spinal cord. Neuroscience 75, 1231–1238 (1996).

    CAS  PubMed  Google Scholar 

  101. Brumovsky, P. et al. The neuropeptide tyrosine Y1R is expressed in interneurons and projection neurons in the dorsal horn and area X of the rat spinal cord. Neuroscience 138, 1361–1376 (2006).

    CAS  PubMed  Google Scholar 

  102. Zhang, X., Tong, Y. G., Bao, L. & Hokfelt, T. The neuropeptide Y Y1 receptor is a somatic receptor on dorsal root ganglion neurons and a postsynaptic receptor on somatostatin dorsal horn neurons. Eur. J. Neurosci. 11, 2211–2225 (1999).

    CAS  PubMed  Google Scholar 

  103. Abe, K. et al. Responses to 5-HT in morphologically identified neurons in the rat substantia gelatinosa in vitro. Neuroscience 159, 316–324 (2009).

    CAS  PubMed  Google Scholar 

  104. Lu, Y. & Perl, E. R. Selective action of noradrenaline and serotonin on neurones of the spinal superficial dorsal horn in the rat. J. Physiol. 582, 127–136 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Gassner, M., Ruscheweyh, R. & Sandkuhler, J. Direct excitation of spinal GABAergic interneurons by noradrenaline. Pain 145, 204–210 (2009).

    CAS  PubMed  Google Scholar 

  106. Sandkuhler, J. Models and mechanisms of hyperalgesia and allodynia. Physiol. Rev. 89, 707–758 (2009). This review provides a detailed and systematic account of the mechanisms that have been proposed to underlie abnormal pain states.

    PubMed  Google Scholar 

  107. Torsney, C. & MacDermott, A. B. Disinhibition opens the gate to pathological pain signaling in superficial neurokinin 1 receptor-expressing neurons in rat spinal cord. J. Neurosci. 26, 1833–1843 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Moore, K. A. et al. Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J. Neurosci. 22, 6724–6731 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Coull, J. A. et al. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 424, 938–942 (2003).

    CAS  PubMed  Google Scholar 

  110. Eaton, M. J., Plunkett, J. A., Karmally, S., Martinez, M. A. & Montanez, K. Changes in GAD- and GABA- immunoreactivity in the spinal dorsal horn after peripheral nerve injury and promotion of recovery by lumbar transplant of immortalized serotonergic precursors. J. Chem. Neuroanat. 16, 57–72 (1998).

    CAS  PubMed  Google Scholar 

  111. Ibuki, T., Hama, A. T., Wang, X. T., Pappas, G. D. & Sagen, J. Loss of GABA-immunoreactivity in the spinal dorsal horn of rats with peripheral nerve injury and promotion of recovery by adrenal medullary grafts. Neuroscience 76, 845–858 (1997).

    CAS  PubMed  Google Scholar 

  112. Azkue, J. J., Zimmermann, M., Hsieh, T. F. & Herdegen, T. Peripheral nerve insult induces NMDA receptor-mediated, delayed degeneration in spinal neurons. Eur. J. Neurosci. 10, 2204–2206 (1998).

    CAS  PubMed  Google Scholar 

  113. Scholz, J. et al. Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve injury. J. Neurosci. 25, 7317–7323 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Whiteside, G. T. & Munglani, R. Cell death in the superficial dorsal horn in a model of neuropathic pain. J. Neurosci. Res. 64, 168–173 (2001).

    CAS  PubMed  Google Scholar 

  115. Polgár, E., Hughes, D. I., Arham, A. Z. & Todd, A. J. Loss of neurons from laminas I–III of the spinal dorsal horn is not required for development of tactile allodynia in the spared nerve injury model of neuropathic pain. J. Neurosci. 25, 6658–6666 (2005).

    PubMed  PubMed Central  Google Scholar 

  116. Polgár, E., Gray, S., Riddell, J. S. & Todd, A. J. Lack of evidence for significant neuronal loss in laminae I–III of the spinal dorsal horn of the rat in the chronic constriction injury model. Pain 111, 144–150 (2004).

    PubMed  Google Scholar 

  117. Polgár, E. & Todd, A. J. Tactile allodynia can occur in the spared nerve injury model in the rat without selective loss of GABA or GABA(A) receptors from synapses in laminae I–II of the ipsilateral spinal dorsal horn. Neuroscience 156, 193–202 (2008).

    PubMed  Google Scholar 

  118. Hwang, J. H. & Yaksh, T. L. The effect of spinal GABA receptor agonists on tactile allodynia in a surgically-induced neuropathic pain model in the rat. Pain 70, 15–22 (1997).

    CAS  PubMed  Google Scholar 

  119. Malan, T. P., Mata, H. P. & Porreca, F. Spinal GABA(A) and GABA(B) receptor pharmacology in a rat model of neuropathic pain. Anesthesiology 96, 1161–1167 (2002).

    CAS  PubMed  Google Scholar 

  120. Schoffnegger, D., Heinke, B., Sommer, C. & Sandkuhler, J. Physiological properties of spinal lamina II GABAergic neurons in mice following peripheral nerve injury. J. Physiol. 577, 869–878 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Bailey, A. L. & Ribeiro-da-Silva, A. Transient loss of terminals from non-peptidergic nociceptive fibers in the substantia gelatinosa of spinal cord following chronic constriction injury of the sciatic nerve. Neuroscience 138, 675–690 (2006).

    CAS  PubMed  Google Scholar 

  122. Castro-Lopes, J. M., Coimbra, A., Grant, G. & Arvidsson, J. Ultrastructural changes of the central scalloped (C1) primary afferent endings of synaptic glomeruli in the substantia gelatinosa Rolandi of the rat after peripheral neurotomy. J. Neurocytol 19, 329–337 (1990).

    CAS  PubMed  Google Scholar 

  123. Ikeda, H., Heinke, B., Ruscheweyh, R. & Sandkuhler, J. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science 299, 1237–1240 (2003).

    CAS  PubMed  Google Scholar 

  124. Ikeda, H. et al. Synaptic amplifier of inflammatory pain in the spinal dorsal horn. Science 312, 1659–1662 (2006). The second of two studies from these authors that demonstrates a form of LTP in lamina I projection neurons — in this case, induced by activation of C fibres at a rate that occurs in physiological conditions.

    CAS  PubMed  Google Scholar 

  125. Bredt, D. S. & Nicoll, R. A. AMPA receptor trafficking at excitatory synapses. Neuron 40, 361–379 (2003).

    CAS  PubMed  Google Scholar 

  126. Esteban, J. A. et al. PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nature Neurosci. 6, 136–143 (2003).

    CAS  PubMed  Google Scholar 

  127. Nagy, G. G. et al. Widespread expression of the AMPA receptor GluR2 subunit at glutamatergic synapses in the rat spinal cord and phosphorylation of GluR1 in response to noxious stimulation revealed with an antigen-unmasking method. J. Neurosci. 24, 5766–5777 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Larsson, M. & Broman, J. Translocation of GluR1-containing AMPA receptors to a spinal nociceptive synapse during acute noxious stimulation. J. Neurosci. 28, 7084–7090 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Randic, M., Jiang, M. C. & Cerne, R. Long-term potentiation and long-term depression of primary afferent neurotransmission in the rat spinal cord. J. Neurosci. 13, 5228–5241 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Ji, R. R., Baba, H., Brenner, G. J. & Woolf, C. J. Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity. Nature Neurosci. 2, 1114–1119 (1999).

    CAS  PubMed  Google Scholar 

  131. Woolf, C. J., Shortland, P. & Coggeshall, R. E. Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 355, 75–78 (1992).

    CAS  PubMed  Google Scholar 

  132. Tong, Y. G. et al. Increased uptake and transport of cholera toxin B-subunit in dorsal root ganglion neurons after peripheral axotomy: possible implications for sensory sprouting. J. Comp. Neurol. 404, 143–158 (1999).

    CAS  PubMed  Google Scholar 

  133. Shehab, S. A., Spike, R. C. & Todd, A. J. Evidence against cholera toxin B subunit as a reliable tracer for sprouting of primary afferents following peripheral nerve injury. Brain Res. 964, 218–227 (2003).

    CAS  PubMed  Google Scholar 

  134. Woodbury, C. J., Kullmann, F. A., McIlwrath, S. L. & Koerber, H. R. Identity of myelinated cutaneous sensory neurons projecting to nocireceptive laminae following nerve injury in adult mice. J. Comp. Neurol. 508, 500–509 (2008).

    PubMed  PubMed Central  Google Scholar 

  135. Neumann, S., Doubell, T. P., Leslie, T. & Woolf, C. J. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons. Nature 384, 360–364 (1996).

    CAS  PubMed  Google Scholar 

  136. Noguchi, K., Dubner, R., De Leon, M., Senba, E. & Ruda, M. A. Axotomy induces preprotachykinin gene expression in a subpopulation of dorsal root ganglion neurons. J. Neurosci. Res. 37, 596–603 (1994).

    CAS  PubMed  Google Scholar 

  137. Malcangio, M., Ramer, M. S., Jones, M. G. & McMahon, S. B. Abnormal substance P release from the spinal cord following injury to primary sensory neurons. Eur. J. Neurosci. 12, 397–399 (2000).

    CAS  PubMed  Google Scholar 

  138. Hughes, D. I., Scott, D. T., Riddell, J. S. & Todd, A. J. Upregulation of substance P in low-threshold myelinated afferents is not required for tactile allodynia in the chronic constriction injury and spinal nerve ligation models. J. Neurosci. 27, 2035–2044 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Baba, H., Doubell, T. P. & Woolf, C. J. Peripheral inflammation facilitates Abeta fiber-mediated synaptic input to the substantia gelatinosa of the adult rat spinal cord. J. Neurosci. 19, 859–867 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Schoffnegger, D., Ruscheweyh, R. & Sandkuhler, J. Spread of excitation across modality borders in spinal dorsal horn of neuropathic rats. Pain 135, 300–310 (2008).

    CAS  PubMed  Google Scholar 

  141. Okamoto, M. et al. Functional reorganization of sensory pathways in the rat spinal dorsal horn following peripheral nerve injury. J. Physiol. 532, 241–250 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Kohno, T., Moore, K. A., Baba, H. & Woolf, C. J. Peripheral nerve injury alters excitatory synaptic transmission in lamina II of the rat dorsal horn. J. Physiol. 548, 131–138 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Schneider, S. P. Functional properties and axon terminations of interneurons in laminae III-V of the mammalian spinal dorsal horn in vitro. J. Neurophysiol. 68, 1746–1759 (1992).

    CAS  PubMed  Google Scholar 

  144. Lima, D., Albino-Teixeira, A. & Tavares, I. The caudal medullary ventrolateral reticular formation in nociceptive-cardiovascular integration. An experimental study in the rat. Exp. Physiol. 87, 267–274 (2002).

    PubMed  Google Scholar 

  145. Boscan, P., Pickering, A. E. & Paton, J. F. The nucleus of the solitary tract: an integrating station for nociceptive and cardiorespiratory afferents. Exp. Physiol. 87, 259–266 (2002).

    PubMed  Google Scholar 

  146. Gauriau, C. & Bernard, J. F. Pain pathways and parabrachial circuits in the rat. Exp. Physiol. 87, 251–258 (2002).

    PubMed  Google Scholar 

  147. Heinricher, M. M., Tavares, I., Leith, J. L. & Lumb, B. M. Descending control of nociception: Specificity, recruitment and plasticity. Brain Res. Rev. 60, 214–225 (2009).

    CAS  PubMed  Google Scholar 

  148. Gauriau, C. & Bernard, J. F. Posterior triangular thalamic neurons convey nociceptive messages to the secondary somatosensory and insular cortices in the rat. J. Neurosci. 24, 752–761 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Wall, P. D. et al. Autotomy following peripheral nerve lesions: experimental anaesthesia dolorosa. Pain 7, 103–111 (1979).

    CAS  PubMed  Google Scholar 

  150. Decosterd, I. & Woolf, C. J. Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 87, 149–158 (2000).

    CAS  PubMed  Google Scholar 

  151. Bennett, G. J. & Xie, Y. K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33, 87–107 (1988).

    CAS  PubMed  Google Scholar 

  152. Kim, S. H. & Chung, J. M. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50, 355–363 (1992).

    CAS  Google Scholar 

  153. Brown, A. G., Fyffe, R. E., Rose, P. K. & Snow, P. J. Spinal cord collaterals from axons of type II slowly adapting units in the cat. J. Physiol. 316, 469–480 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Light, A. R. & Perl, E. R. Spinal termination of functionally identified primary afferent neurons with slowly conducting myelinated fibers. J. Comp. Neurol. 186, 133–150 (1979).

    CAS  PubMed  Google Scholar 

  155. Shortland, P., Woolf, C. J. & Fitzgerald, M. Morphology and somatotopic organization of the central terminals of hindlimb hair follicle afferents in the rat lumbar spinal cord. J. Comp. Neurol. 289, 416–433 (1989).

    CAS  PubMed  Google Scholar 

  156. Lorenzo, L. E., Ramien, M., St. Louis, M., De Koninck, Y. & Ribeiro-da-Silva, A. Postnatal changes in the Rexed lamination and markers of nociceptive afferents in the superficial dorsal horn of the rat. J. Comp. Neurol. 508, 592–604 (2008).

    PubMed  Google Scholar 

  157. Todd, A. J. & Koerber, H. R. in Wall and Melzack's Textbook of Pain 5th Edition (Eds McMahon, S. & Koltzenburg, M.) 73–90 (Elsevier, Edinburgh, 2005).

    Google Scholar 

  158. Todd, A. J. in Handbook of Clinical Neurology 3rd Series, Pain. (Eds Cervero, F. and Jensen, T. S.) 61–76 (Elsevier, Edinburgh, 2006).

    Google Scholar 

  159. Todd, A. J. in Current Topics in Pain: 12th World Congress on Pain (Ed. Castro-Lopes, J.) 25–51 (IASP Press, Seattle, 2009).

    Google Scholar 

Download references

Acknowledgements

Support from the Wellcome Trust is gratefully acknowledged. I also thank T. Yasaka, D.I. Hughes and E. Polgár for helpful discussion and advice.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andrew J. Todd.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Andrew J. Todd's homepage

Glossary

Nocifensive reflex

A protective reflex generated in response to a damaging (or potentially damaging) stimulus.

Allodynia

Pain following a normally non-painful tactile or thermal stimulus.

Neuropathic pain

Pain resulting from pathology of the nervous system. Most commonly this is caused by conditions affecting peripheral nerves.

Nociceptive information

Stimuli through which we perceive damage (or potential damage) caused to the body by excessive heat, cold or physical injury, for example.

Laminae of Rexed

A system of 10 layers, described by Rexed, to divide the grey matter in the spinal cord.

Synaptic glomerulus

A complex structure in which a central axonal bouton (of primary afferent origin) is in synaptic contact with several surrounding profiles, including dendrites and peripheral axons.

Nucleus raphe magnus

The main source of descending serotonergic axons that innervate the dorsal horn.

Locus coeruleus

The major source of noradrenergic axons to the spinal cord.

Volume transmission

A form of neurotransmission in which a neurotransmitter is released directly into the non-synaptic extracellular space to activate nearby receptors.

Rostral ventromedial medulla

A region of the brainstem that includes the nucleus raphe magnus and gives rise to many descending axons that innervate the dorsal horn.

Delayed firing pattern

A response to injected depolarizing current in which a neuron generates action potentials after a delay.

Gap firing pattern

A response to injected depolarizing current in which an initial action potential is followed by a long inter-spike interval and then regular firing.

Reluctant firing pattern

This term is used to describe neurons that are resistant to action potential firing during injection of depolarizing current.

Hyperalgesia

Exaggerated pain in response to a noxious stimulus.

Transient receptor potential A1

(Often abbreviated to TRPA1.) A non-selective cation channel that is activated by cold and by various chemical irritants (including mustard oil), and that is expressed by certain nociceptive primary afferents (a subset of those that express transient receptor potential V1).

Transient receptor potential vanilloid1

(Often abbreviated to TRPV1.) A non-selective cation channel that can be activated by various noxious stimuli (including heat and application of capsaicin) and that is expressed by many nociceptive primary afferents.

Long-term potentiation

(Often abbreviated to LTP.) A form of synaptic plasticity that results in a long-lasting increase in the strength of synaptic transmission.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Todd, A. Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci 11, 823–836 (2010). https://doi.org/10.1038/nrn2947

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2947

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing