Neuropathic pain

Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system, rather than by stimulation of pain receptors by tissue damage (IASP, 2023). It is a clinical condition rather than a specific molecular target, characterized by symptoms such as allodynia, hyperalgesia, and spontaneous burning sensations (StatPearls, 2023). The underlying pathophysiology involves maladaptive plasticity in the nervous system, including peripheral sensitization, ectopic activity in damaged axons, and central sensitization within the spinal cord dorsal horn (PubMed, PMID: 24333055). Because neuropathic pain involves a variety of signaling disruptions, pharmacological treatment focuses on modulating diverse molecular targets such as voltage-gated calcium channels (targeted by gabapentinoids) and monoamine transporters (targeted by SNRIs and TCAs) (Mayo Clinic, 2023). While these drugs provide relief for many, they often come with significant dose-limiting side effects like somnolence and dizziness, and many patients fail to achieve adequate pain control (NIH, 2023). Identifying specific molecular drivers in individual patients remains a major challenge in the development of targeted analgesics (Nature Reviews Disease Primers, 2017).

Other names

NeuralgiaNerve painNeuropathic pain syndromePeripheral neuropathyCentral pain syndrome

Therapeutic agents for this condition act through various mechanisms including the inhibition of the alpha-2-delta subunit of voltage-gated calcium channels, inhibition of serotonin and norepinephrine reuptake to enhance descending inhibitory pathways, and blockade of voltage-gated sodium channels to reduce ectopic neuronal firing.