Location, Location, Location?

Pain is a useful sensation. Nociceptive pain provides warning of impending or actual tissue damage and prompts aversive or attentive actions that protect the body from harm. People who do not feel pain, due to mutation of certain ion channels (1), suffer a lifetime of otherwise avoidable injuries. The consequences of losing the ability to feel pain also are highlighted by the symptoms and clinical outcomes of diabetic neuropathy. Sensory neuropathy, in conjunction with vascular disease and impaired wound healing, leads to unattended lesions and ulcers, infection, and amputation (2). However, despite having a predominant neuropathy phenotype of degeneration and sensory loss, a proportion of people with diabetes also report spontaneous tingling, pricking, and pain sensations (3). This neuropathic pain is an enigmatic and disruptive symptom that adds psychological insult to the physical injury of progressive nerve degeneration. The prevalence of neuropathic pain is frequently underestimated, but a recent community-based study found that pain was reported by a third of all participants (4). There are currently only three FDA-approved treatments for painful diabetic neuropathy: the anticonvulsant pregabalin, the serotonin–norepinephrine reuptake inhibitor (SNRI) duloxetine, and the opioid/SNRI tapentadol. All are used to treat diverse pain conditions, are likely to suppress pain perception rather than intervene in pathogenic mechanisms of painful diabetic neuropathy, and have undesirable side effects. None …