Pain vulnerability: a neurobiological perspective

Abstract

There are many known risk factors for chronic pain conditions, yet the biological underpinnings that link these factors to abnormal processing of painful signals are only just beginning to be explored. This Review will discuss the potential mechanisms that have been proposed to underlie vulnerability and resilience toward developing chronic pain. Particular focus will be given to genetic and epigenetic processes, priming effects on a cellular level, and alterations in brain networks concerned with reward, motivation/learning and descending modulatory control. Although research in this area is still in its infancy, a better understanding of how pain vulnerability emerges has the potential to help identify individuals at risk and may open up new therapeutic avenues.

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Figure 1: Various risk factors have been identified for chronic pain, such as genetic, environmental and personality factors.
Figure 2: Polymorphisms in the DNA sequence and epigenetic mechanisms such as DNA methylation and histone modifications determine some risk from birth that can lead to transcriptome and connectivity differences.
Figure 3: Adverse events, such as stress, injury or disease, can challenge and modify the hardwired system at different levels, including epigenetic, cell biological, and systems and network levels.
Figure 4: Various brain networks may be involved in conferring vulnerability to painful conditions, particularly the reward-motivation network (purple regions) and the DPMS (green regions).

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Acknowledgements

The authors are supported by grants from the Wellcome Trust.

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Denk, F., McMahon, S. & Tracey, I. Pain vulnerability: a neurobiological perspective. Nat Neurosci 17, 192–200 (2014). https://doi.org/10.1038/nn.3628

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