Nociceptor sensitization in pain pathogenesis

Abstract

The incidence of chronic pain is estimated to be 20–25% worldwide. Few patients with chronic pain obtain complete relief from the drugs that are currently available, and more than half report inadequate relief. Underlying the challenge of developing better drugs to manage chronic pain is incomplete understanding of the heterogeneity of mechanisms that contribute to the transition from acute tissue insult to chronic pain and to pain conditions for which the underlying pathology is not apparent. An intact central nervous system (CNS) is required for the conscious perception of pain, and changes in the CNS are clearly evident in chronic pain states. However, the blockage of nociceptive input into the CNS can effectively relieve or markedly attenuate discomfort and pain, revealing the importance of ongoing peripheral input to the maintenance of chronic pain. Accordingly, we focus here on nociceptors: their excitability, their heterogeneity and their role in initiating and maintaining pain.

Etiology and Pharmacology of Neuropathic Pain

“…The intrinsic properties of dorsal horn neurons such as rheobase, threshold, excitability, and/or input resistance are little changed by peripheral nerve injury (Balasubramanyan et al, 2006). This finding is consistent with the likelihood that ongoing ectopic activity in peripheral nerves is required to drive and maintain central sensitization (Devor, 2006;Pitcher and Henry, 2008;Gold and Gebhart, 2010;Vaso et al, 2014;Daou et al, 2016;Sexton et al, 2017).…”

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

“…They can be sensitized, which is one of the critical mechanisms behind neuropathic pain (37,38). Previous studies have observed that changes in the expression of voltage-gated sodium channel 1.8 and tissue inhibitors of metalloproteinase (TIMPs) occurred in the DRG of rats in a neuropathic pain model (39,40).…”

Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets

“…Moreover, additional changes may involve the dysregulation of the inhibitory interneurons in the dorsal horn and the descending modulatory pathways, glial cell reactivation following the synthesis and release of proinflammatory cytokines and, finally, a morphological and functional reorganization of the afferent projections in the dorsal horn. [15][16][17][18] Despite the fact that neuropathic pain physiopathology has been thoroughly studied, a detailed study focusing on the plastic processes affecting nociceptive neurons in an injured somatosensorial system could involve a double implication: (1) a novel approach in the identification of either molecular or cellular targets involved in neuropathic pain; and (2) it could also shed some light in the design of new therapeutic strategies for neuropathic pain states. Therefore, the aim of the present review is to look over the molecular and biochemical neuroplasticity changes that occur in the somatosensory system during the development of neuropathic pain.…”