Entanglement between thermoregulation and nociception in the rat: the case of morphine.
In thermoneutral conditions, rats display cyclic variations of the vasomotion of the tail and paws, the most widely used target organs in current acute or chronic animal models of pain. Systemic morphine elicits their vasoconstriction followed by hyperthermia in a naloxone-reversible and dose-dependent fashion. The dose-response curves were steep with ED50in the 0.5-1 mg/kg range. Given the pivotal functional role of the rostral ventromedial medulla (RVM) in nociception and the rostral medullary raphe (rMR) in thermoregulation, two largely overlapping brain regions, the RVM/rMR was blocked by muscimol: it suppressed the effects of morphine. "On-" and "off-" neurons recorded in the RVM/rMR are activated and inhibited by thermal nociceptive stimuli, respectively. They are also implicated in regulating the cyclic variations of the vasomotion of the tail and paws seen in thermoneutral conditions. Morphine elicited abrupt inhibition and activation of the firing of on- and off-cells recorded in the RVM/rMR. By using a model that takes into account the power of the radiant heat source, initial skin temperature, core body temperature, and peripheral nerve conduction distance, one can argue that the morphine-induced increase of reaction time is mainly related to the morphine-induced vasoconstriction. This statement was confirmed by analyzing in psychophysical terms the tail-flick response to random variations of noxious radiant heat. Although the increase of a reaction time to radiant heat is generally interpreted in terms of analgesia, the present data question the validity of using such an approach to build a pain index.
Sorbonne Universités, Université Pierre et Marie Curie, Faculté de Médecine, Paris, France; and.|Neurosciences Paris-Seine, Institut National de la Santé et de la Recherche Médicale UMRS-1130, Centre National de la Recherche Scientifique UMR-8246, Paris, France.
Nabil
N
El Bitar
Sorbonne Universités, Université Pierre et Marie Curie, Faculté de Médecine, Paris, France; and.|Neurosciences Paris-Seine, Institut National de la Santé et de la Recherche Médicale UMRS-1130, Centre National de la Recherche Scientifique UMR-8246, Paris, France.
Bernard
B
Pollin
Sorbonne Universités, Université Pierre et Marie Curie, Faculté de Médecine, Paris, France; and.|Neurosciences Paris-Seine, Institut National de la Santé et de la Recherche Médicale UMRS-1130, Centre National de la Recherche Scientifique UMR-8246, Paris, France.
Elias
E
Karroum
Sorbonne Universités, Université Pierre et Marie Curie, Faculté de Médecine, Paris, France; and.|Neurosciences Paris-Seine, Institut National de la Santé et de la Recherche Médicale UMRS-1130, Centre National de la Recherche Scientifique UMR-8246, Paris, France.
Ivanne
I
Pincedé
Sorbonne Universités, Université Pierre et Marie Curie, Faculté de Médecine, Paris, France; and daniel.le_bars@upmc.fr.|Neurosciences Paris-Seine, Institut National de la Santé et de la Recherche Médicale UMRS-1130, Centre National de la Recherche Scientifique UMR-8246, Paris, France.
Daniel
D
Le Bars
D000200:Action Potentials / Q000187:drug effects; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D066267:Midbrain Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009020:Morphine / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D059225:Nociception / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012881:Skin Temperature / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000701:Analgesics, Opioid; D058785:GABA-A Receptor Agonists; D009292:Narcotic Antagonists; D009118:Muscimol; D009270:Naloxone; D009020:Morphine
blood pressure; core temperature; heart rate; morphine; rat; rostral medullary raphe; rostral ventromedial medulla; skin temperature; thermoregulation