Untangling neuropathic pain: pathophysiological insights and future directions for targeted therapy
Naunyn Schmiedebergs Arch Pharmacol. 2026 May 30. doi: 10.1007/s00210-026-05478-4. Online ahead of print.
ABSTRACT
The primary objective of this study is to investigate the intricate underlying mechanisms of neuropathic pain using a multifaceted framework which includes cellular, molecular, and systems-level perspectives as well as molecular targets for establishing the customised pain relief strategies to improve clinical outcomes. In order to provide an in-depth understanding of neuropathic pain processes as well as treatment approaches, this review addresses research in molecular biology, neurophysiology and molecular mechanisms including neurotransmitter modifications, ion channel failure, and gene expression changes along with current developments in emerging pharmacological and non-pharmacological therapies, relying on peer-reviewed studies, experimental research, and clinical trials. The review reveals that neuropathic pain is driven by several distinct pathways rather than a single pathological process. Significant findings demonstrate that altered ion channel activity, neurotransmitter dysregulation, inflammation, microglial activation and oxidative stress contribute to pain persistence. Current treatments, including antidepressants and opioids, provide limited relief and can cause side effects, whereas non-pharmacological methods offer supportive advantages. Neuropathic pain is a complex condition influenced by neurobiological changes at molecular, cellular, and systemic levels. Understanding of these pathways is essential for creating personalised medicines that go beyond conventional symptomatic relief. Enhancing pain management and improving patient quality of life may be possible with new molecular targets and integrated therapy approaches. In order to reduce the worldwide burden of chronic neuropathic pain, future research must concentrate on transforming molecular findings into practicable therapeutic approaches.
PMID:42217042 | DOI:10.1007/s00210-026-05478-4