Pain modulation by release of the endogenous cannabinoid anandamide

Synthetic cannabinoids produce behavioral analgesia and suppress pain neuro transmission, raising the possibility that endogenous cannabinoids serve na turally to modulate pain. Here, the development of a sensitive method for m easuring cannabinoids by atmospheric pressure-chemical ionization mass spec trometry permitted measurement of the release of the endogenous cannabinoid anandamide in the periaqueductal gray (PAC) by in vivo microdialysis in th e rat. Electrical stimulation of the dorsal and lateral PAG produced CB1 ca nnabinoid receptor-mediated analgesia accompanied by a marked increase in t he release of anandamide in the PAG, suggesting that endogenous anandamide mediates the behavioral analgesia. Furthermore, pain triggered by subcutane ous injections of the chemical irritant formalin substantially increased th e release of anandamide in the PAC. These findings indicate that the endoge nous cannabinoid anandamide plays an important role in a cannabinergic pain -suppression system existing within the dorsal and lateral PAG. The existen ce of a cannabinergic pain-modulatory system may have relevance for the tre atment of pain, particularly in instances where opiates are ineffective.