Τετάρτη 7 Σεπτεμβρίου 2016

Entanglement between Thermoregulation and Nociception in the rat: The case of Morphine

In thermal neutral condition, 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-dependant fashion. The dose-response curves were steep with ED50 in the 0.5-1 mg/kg range. Given the pivotal functional role of Rostral Ventro-medial Medulla (RVM) in nociception and 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 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 thermal neutral condition. 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, the initial skin temperature, the core body temperature and the 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.



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