Antinociception and Suppression of Pain Neurotransmission by Systemically Administered Cannabinoids

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Cannabinoid antinociception is observed in preclinical behavioral studies employing different modalities of noxious stimulation including thermal, mechanical, and chemical (see Walker et al. 2001 for review). Perhaps the earliest recorded scientific demonstration of cannabinoid antinociception was provided by one of the fathers of modern pharmacology, Ernest Dixon (1899). He observed that dogs that inhaled cannabis smoke failed to react to pin pricks. Early studies by Bicher and Mechoulam (1968) and Kosersky et al. (1973) provided a foundation for subsequent work that verifiedthe abilityofcannabinoidstoprofoundlysuppressbehavioralre-actions to acute noxious stimuli and inflammatory and nerve injury-induced pain. In these early studies, it was noted that the potency and efficacy of cannabinoids rival that of morphine (Bloom et al. 1977; Buxbaum 1972). However, cannabinoids also produce profound motor effects [e.g., immobility, catalepsy; (Martin et al. 1991)], a potential confound for behavioral studies, which inevitably employ motor responses to noxious stimuli as a measure of pain sensitivity.

In part to address this potential confound, subsequent electrophysiological and neurochemical studies examined the question of whether cannabinoids suppress activity within pain circuits. These studies provided convincing evidence that cannabinoids suppress nociceptive transmission in vivo (see Hohmann 2002 for review). Walker's laboratory first demonstrated that cannabinoids suppress noxious stimulus-evoked neuronal activity in nociceptive neurons in the spinal cord (Fig. 2)

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