Tissue injury prompts the release of a number of proalgesic molecules that induce acute and chronic pain by sensitizing pain-sensing neurons (nociceptors) to heat and mechanical stimuli. In contrast, many proalgesics have no effect on cold sensitivity, or can inhibit cold-sensitive neurons and diminish cooling-mediated pain-relief (analgesia). Nonetheless, cold pain (allodynia) is prevalent in many inflammatory and neuropathic pain settings, with little known of the mechanisms promoting pain versus those dampening analgesia. This disclosure establishes provides methods and compositions to treat cold allodynia induced by inflammation, nerve injury, and chemotherapeutics. One such therapy is the administration of antibodies against the GFRα3 ligand, artemin.
