title: Pharmacological dissection of the paradoxical pain induced by a thermal grill.
abstract: We investigated the role of the glutamatergic and endogenous opioidergic systems in the paradoxical pain evoked by the simultaneous application of innocuous warm and cold stimuli to the skin with a "thermal grill". Two parallel randomized, double-blind, cross-over studies, including two groups of 12 healthy volunteers, were carried out to compare the effects of i.v. ketamine or naloxone to those of placebo, on the sensations produced by a thermode (i.e. thermal grill) composed of six bars applied on the palmar surface of the right hand. The temperature of alternate (even- and odd-numbered) bars could be controlled independently by Peltier elements to produce various patterns of the grill. During each experimental session we measured the effects of ketamine, naloxone or placebo on the intensity of: (i) paradoxical pain; (ii) "normal" thermal (heat and cold) pain; and (iii) non-painful thermal (warm and cool) sensations. Ketamine administration resulted in a significant reduction of paradoxical pain intensity but did not alter normal pain or non-painful thermal sensations. By contrast, naloxone had no effect on paradoxical pain, normal pain or non-painful thermal sensations. This study demonstrates for the first time that the "thermal grill illusion of pain" can be modulated pharmacologically. This paradoxical pain, which involves the glutamatergic systems, acting through the NMDA receptors, but not the tonic endogenous opioids systems, might share some mechanisms with pathological pain.
authors.affiliation: INSERM U-792, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, 9, Avenue Charles de Gaulle, Boulogne-Billancourt F-92100, France Université Versailles-Saint-Quentin, Versailles F-78035, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Kern
authors.forename: Emilie
authors.initials: E
authors.lastname: Pelle-Lancien
authors.forename: Virginie
authors.initials: V
authors.lastname: Luce
authors.forename: Didier
authors.initials: D
authors.lastname: Bouhassira
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D003080:Cold Temperature / Q000009:adverse effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D007088:Illusions / Q000187:drug effects / Q000502:physiology*; D007649:Ketamine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D018847:Opioid Peptides / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010148:Intractable Pain / Q000378:metabolism / Q000503:physiopathology; D010919:Placebos; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology*
chemical_list: D000700:Analgesics; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010919:Placebos; D017470:Receptors, Glutamate; D011957:Receptors, Opioid; D009270:Naloxone; D018698:Glutamic Acid; D007649:Ketamine