Rethinking morphine for neuropathic pain in the elderly: a neuroimmune perspective on preclinical evidence and clinical caution

Managing neuropathic pain in older adults is a major clinical challenge. This commentary synthesizes emerging preclinical and clinical evidence on a critical concern: morphine, a cornerstone opioid analgesic, may paradoxically exacerbate neuropathic pain in the aging population. In the context of an age-related pro-inflammatory state (neuroinflammatory priming) and altered μ-opioid receptor (MOR) function, chronic morphine administration can activate glial cells (microglia and astrocytes), elevate pro-inflammatory cytokines, and induce opioid-induced hyperalgesia (OIH). This evidence challenges the traditional view of morphine as a neutral analgesic and reframes it as a potential modulator of the neuropathic pain cycle in the vulnerable aged nervous system. Consequently, a paradigm shift in clinical practice is warranted. We argue for prioritizing multimodal, non-opioid strategies ( e.g. , gabapentinoids, SNRIs), employing extreme caution with opioid prescribing using a "start low, go slow" approach, and integrating comprehensive geriatric assessment to guide safer therapeutic decision-making for the elderly. Keywords: Morphine, neuropathy, aging, neuroinflammation, chronic pain