Neuropathic pain: role of inflammation, immune response, and ion channel activity in central injury mechanisms

Abstract

Neuropathic pain (NP) is a significant and disabling clinical problem with very few therapeutic treatment options available. A major priority is to identify the molecular mechanisms responsible for NP. Although many seemingly relevant pathways have been identified, more research is needed before effective clinical interventions can be produced. Initial insults to the nervous system, such as spinal cord injury (SCI), are often compounded by secondary mechanisms such as inflammation, the immune response, and the changing expression of receptors and ion channels. The consequences of these secondary effects myriad and compound those elicited by the primary injury. Chronic NP syndromes following SCI can greatly complicate the clinical treatment of the primary injury and result in high comorbidity. In this review, we will describe physiological outcomes associated with SCI along with some of the mechanisms known to contribute to chronic NP development.

Gabexate mesilate ameliorates the neuropathic pain in a rat model by inhibition of proinflammatory cytokines and nitric oxide pathway via suppression of nuclear factor-κB

“…During the process of neuroinflammation, NO is released into the dorsal horn of the spinal cord [35,41]. As inflammatory and proinflammatory mediators are upregulated during chronic inflammation, the primary active form of NO (iNOS) is induced [19,42]. NO reacts with superoxide and produces peroxynitrite, which leads to central sensitization consequently by enhancing phosphorylation of N-methyl-D-aspartate receptors [43].…”

“…However, the consequent inhibition of expressions of proinflammatory cytokines (IL-1, IL-6, and TNF-α) lasted only for a week. The reason for the inconsistency is unclear but is thought to be due to the involvement of several mechanisms in the development of neuropathic pain [42].…”

Inducible nitric oxide synthase inhibition by 1400W limits pain hypersensitivity in a neuropathic pain rat model

“…However, preclinical studies using animal models of PNP, including the L5 spinal nerve axotomy (SNA) rat model (Kim & Chung, ), suggest that PNP is attributable to sensitization of both primary afferent nociceptive neurons (peripheral sensitization) and CNS neurons (central sensitization; Campbell & Meyer, ; Costigan, Scholz, & Woolf, ; von Hehn, Baron, & Woolf, ). Numerous inflammatory mediators, often termed ‘sensitizers’, including pro‐inflammatory cytokines and reactive oxygen and nitrogen species (ROS/RNS) such as nitric oxide (NO), contribute to peripheral and central sensitization (Kim, Kim, Han, Choe, & Ahn, ; Ren & Dubner, ; Schomberg, Ahmed, Miranpuri, Olson, & Resnick, ).…”

Potential for endocannabinoid system modulation in ocular pain and inflammation: filling the gaps in current pharmacological options

“…Inflammatory pain is a form of nociceptive pain. The process of inflammation can, however, itself lead to the development of neuropathic pain [67][68][69][70][71]. This inflammatory neuronal damage can occur directly, such as in autoimmune neuropathy, or indirectly, such as from nerve compression, which may result in ischemic nerve injury.…”