Ventrolateral periaqueductal gray exogenous and endogenous histamine attenuates sciatic nerve chronic constriction injury-induced neuropathic pain through opioid receptors

The aim of the present study was to investigate the effects of intra-ventrolateral periaqueductal gray (vlPAG) microinjection of histamine and thioperamide (a histamine H3 receptor antagonist/inverse agonist) on neuropathic pain. To explore the possible mechanism, naloxone was microinjected alone or in combination with histamine and thioperamide. Neuropathic pain was induced by the left sciatic nerve chronic constriction injury. Both the right and left sides of vlPAG of the brain were surgically cannulated. Cold allodynia and mechanical hyperalgesia were recorded by acetone evaporation and Von Frey filament tests. Areas under curve of allodynia and hyperalgesia were calculated. Histamine (0.50 and 2.00 µg site-1), thioperamide (4.00 µg site-1) and thioperamide (4.00 µg site-1) before histamine (2.00 µg site-1) suppressed cold allodynia and mechanical hyperalgesia after microinjection into the vlPAG. Microinjection of naloxone (0.25 and 1.00 µg site-1) into the vlPAG had no effect on cold allodynia and mechanical hyperalgesia. The anti-allodynic and anti-hyperalgesic effects induced by microinjection of histamine (2.00 µg site-1) and thioperamide (4.00 µg site-1) into the vlPAG were inhibited by prior microinjection of naloxone (1.00 µg site-1) into the same site. The above-mentioned drugs did not alter locomotor activity. Based on our present results, it is concluded that exogenous (by histamine microinjection) and endogenous (by thioperamide microinjection) histamine of the vlPAG may contribute to the descending pain control mechanisms through a naloxone-sensitive mechanism.