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Plasticity in ventral pallidal cholinergic neuron-derived circuits contributes to comorbid chronic pain-like and depression-like behaviour in male mice
The cholinergic circuits involved in pain modulation remain poorly understood. Here, the authors show that reversal of plasticity in the ventral pallidum-basolateral amygdala cholinergic pathway relieves hyperalgesia and depression-like behaviours in a chronic pain mouse model.
- Ya-Wei Ji
- , Zi-Lin Shen
- & Cheng Xiao
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Article
| Open Access
A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors
Maladaptive plastic changes in the brain are critical for pain maintenance. The authors identify a nigro–subthalamo–parabrachial pathway and reveal that reversing a series of neuronal and synaptic malfunctions in this pathway in acute and chronic pain mitigates hyperalgesia, providing potential therapeutic targets for pain modulation.
- Tao Jia
- , Ying-Di Wang
- & Chunyi Zhou
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Article
| Open Access
Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain
Microglia subpopulations may differentially contribute to pain. Here, the authors show that peripheral nerve injury induces time- and sex-specific transcriptional changes in mouse spinal cord microglia subpopulations and that ApoE is linked to neuropathic pain hypersensitivity in mice and humans.
- Shannon Tansley
- , Sonali Uttam
- & Arkady Khoutorsky
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Article
| Open Access
MicroRNA cluster miR-17-92 regulates multiple functionally related voltage-gated potassium channels in chronic neuropathic pain
Dysregulation of voltage gated potassium channels is a feature of neuropathic pain. Here in a rat model the authors identify the microRNA cluster miR-17-92 as a regulator of voltage gated potassium channels in the dorsal root ganglion neurons.
- Atsushi Sakai
- , Fumihito Saitow
- & Hidenori Suzuki
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Article
| Open Access
DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons
Transcriptional changes occur in the dorsal root ganglion in response to nerve injury and may contribute to neuropathic pain. Here the authors show that the DNA methyltransferase DNMT3a is upregulated in rodents following nerve injury, and may contribute to pain-like behaviour by decreasing expression of the voltage-gated potassium channel Kv1.2.
- Jian-Yuan Zhao
- , Lingli Liang
- & Yuan-Xiang Tao
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| Open Access
Induced sensorimotor brain plasticity controls pain in phantom limb patients
Pain in a phantom limb after limb deafferentation may be due to maladaptive sensorimotor representation. Here the authors find that sensorimotor plasticity induced by BMI training with the phantom hand, contrary to expectation, increased pain while dissociating prosthetic movements from the phantom arm relieved the pain.
- Takufumi Yanagisawa
- , Ryohei Fukuma
- & Youichi Saitoh
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| Open Access
Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia
Neuropathic pain hypersensitivity is known to undergo diurnal variations, although the underlying mechanisms are not clear. Using a sciatic nerve-injury mouse model, the authors find such diurnal changes are mediated by glucocorticoid induced enhancement of ATP release from astrocytes via pannexin-1 hemichannels.
- Satoru Koyanagi
- , Naoki Kusunose
- & Shigehiro Ohdo
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Article
| Open Access
Intracellular mGluR5 plays a critical role in neuropathic pain
mGluR5 has been shown to play a role in chronic pain regulation. Here, the authors use membrane permeable and non-transported, impermeable mGluR5 antagonists to show that spinal analgesic effects in vivoare mediated by intracellular rather than cell surface mGluR5.
- Kathleen Vincent
- , Virginia M. Cornea
- & Terence J. Coderre
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| Open Access
Oligodendrocyte ablation triggers central pain independently of innate or adaptive immune responses in mice
Whether oligodendrocytes have a role in the development of chronic pain is not clear. Here the authors show that oligodendrocyte depletion causes a neuropathic pain that sets in before demyelination and is independent of immune cell activation and infiltration.
- Simon Gritsch
- , Jianning Lu
- & Rohini Kuner
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Article
| Open Access
Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction
Disinhibition of neural activity in the spinal cord is implicated in neuropathic pain. Chen et al.show that disinhibition of neural activity arises from a shift in reversal potential of GABA and a decrease in the conductance of presynaptic GABA, which are both regulated by brain-derived neurotrophic factor.
- Jeremy Tsung-chieh Chen
- , Da Guo
- & Jing Hu
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Article
| Open Access
Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain
In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of proteins, such as the purinergic P2X4 receptor. Here, Masuda et al.show that the transcription factor axis, interferon regulatory factor-8 and -5, drives the expression of P2X4 receptor in microglia and the adoption of a reactive phenotype after peripheral nerve injury.
- Takahiro Masuda
- , Shosuke Iwamoto
- & Kazuhide Inoue
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Article
| Open Access
Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons
Sodium channel Nav1.7 is essential for acute human pain but its role in chronic neuropathic pain is unclear. Minett and colleagues show that Nav1.7 expression specifically in sympathetic neurons, rather than sensory neurons, is required for the development of chronic neuropathic pain after injury.
- Michael S. Minett
- , Mohammed A. Nassar
- & John N. Wood
NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice