Neuropathic pain pharmacotherapy: Mechanisms, anti-inflammatory actions, and clinical perspectives

Neuropathic pain (NP) is a chronic pain condition resulting from injury or disease of the somatosensory nervous system. NP is frequently intractably resistant to conventional analgesics and increasingly implicated in neuroimmune imbalances and ongoing neuroinflammatory activity. First-line pharmacological treatments for NP are certain antidepressants and gabapentinoid anticonvulsants that, if anything, not only regulate neuronal communication but also are anti-inflammatory. Opioid analgesics and cannabinoid-containing medications are second- or third-line for refractory instances, yet long-term safety and efficacy are of concern. A narrative review was conducted of more recent clinical trials (2018-present) and mechanistic investigations of treatments for NP. Antidepressants (e.g., tricyclic antidepressants and SNRIs) are effective in numerous NP conditions and appear to inhibit pro-inflammatory cytokine activity. Gabapentinoids (gabapentin, pregabalin) have considerable value for pain relief in a subset of patients through the inhibition of neuronal excitability and the induction of anti-inflammatory cytokines. Opioids provide relief for short-term NP in some patients, but usefulness is limited by lack of sustained benefit, possible tolerance, and opioid-induced hyperalgesia with glial activation. Cannabinoids are now an adjunct treatment with modest analgesic efficacy and notable side effects; they probably modulate NP via both central and immune mechanisms. In summary, effective NP management is generally a question of multimodal pharmacotherapy that targets both neural hyperexcitability and neuroinflammation. Additional research on the neuroimmune mechanisms of NP could lead to the creation of safer and more efficacious analgesics.