Clinical and animal data suggest that antihistamines may have efficacy in t
he management of pain. While many mechanisms of action have been proposed f
or the analgesic action of antihistamines, the exact mechanism is unknown.
Controlled clinical trials in different pain models have demonstrated that
antihistamines have direct and adjuvant analgesic activity. We report three
patients with advanced cancer pain refractory to adjuvants and oral, intra
venous, and epidural opioids, who achieved sustained pain relief after the
repeated administration of diphenhydramine. Diphenhydramine may be useful i
n the treatment ly neuropathic and nociceptive pain that has failed to resp
ond to treatment with opioids and adjuvant analgesics. We suggest a startin
g dose of 25 mg of oral or parenteral. diphenhydramine every 6 to 8 hours,
with titration to effect. (C) U.S. Cancer Pain Relief Committee, 2001.