Neurosensory changes in a human model of endothelin-1 induced pain: a behavioral study.
Although pain is a frequent feature in patients with cancer, its etiology is still poorly understood. In recent years, endothelin-1 (ET-1) has become a major target molecule in the etiology of cancer pain. In this randomised, double-blind study the effects of intradermal injection of ET-1 on spontaneous pain, temperature perception and sensation of punctate stimulation were evaluated. Thirty-five subjects were randomised to receive either placebo or one of four concentrations of ET-1 (ranging from 10(-10) to 10(-6)M). Besides assessment of spontaneous pain, three neurosensory testings were performed: (1) cold and warm sensation, (2) cold and heat pain, and (3) punctate stimulation using a von Frey monofilament. ET-1 produced a dose-dependent flare zone that was absent after placebo injection. Subjects reported a short-lasting spontaneous pain upon administration of the highest concentrations of ET-1. Injection of ET-1 induced a long-lasting and dose-dependent punctate hyperalgesia in an area around the injection site (secondary hyperalgesia). Thermal testing revealed a short period of hypoesthesia to non-noxious warm and cold stimuli after some doses of ET-1. In addition to the mechanical hyperalgesia, intradermal injection of ET-1 almost instantaneously induced a state of cold hyperalgesia outlasting the study period (120 min). No development of heat hyperalgesia was observed. The observed psychophysical characteristics of this new model of ET-1 induced nociception indicate its potential as a human experimental model for cancer pain.
Hans
Guy
G
Multidisciplinary Pain Center, Antwerp University Hospital, Edegem, Belgium. guy.hans@uza.be
Deseure
Kristof
K
Robert
Dominique
D
De Hert
Stefan
S
D000328:Adult; D001519:Behavior / Q000187:drug effects / Q000502:physiology; D001703:Biophysics / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000009:adverse effects / Q000378:metabolism*; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D007271:Injections, Intradermal / Q000009:adverse effects; D008297:Male; D008959:Models, Neurological; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D044022:Receptor, Endothelin A / Q000819:agonists / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000503:physiopathology; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D044022:Receptor, Endothelin A