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The present study investigated whether spinal astrocyte and microglia were activated in Buthus martensi Karch (BmK) venom-induced rat pain-related behaviors. The results showed that glial fibrillary acidic protein (GFAP) immunoreactivity indicative astrocyte activation in bilateral spinal cord started to increase by day 3, peaked at day 7 and gradually reversed at day 14 following intraplantar injection of BmK venom. Western blotting analysis confirmed GFAP expression was up-regulated by BmK venom. In contrast, bilateral spinal increase of OX-42 immunoreactivity indicative of microglial activation began at 4h peaked at day 1 and gradually reversed by days 3 to 7 after the administration of BmK venom. Pretreatment with either intrathecal injection of fluorocitrate or intraperitonial injection of minocycline, and two glial activation inhibitors, suppressed the spontaneous nociceptive responses, and prevented the primary thermal and bilateral mechanical hyperalgesia induced by BmK venom. The post-treatment with fluorocitrate or minocycline could not affect the mechanical hyperalgesia. Moreover, minocycline partially inhibited BmK venom-induced spinal c-Fos expression but lack of effects on BmK venom-induced paw edema. Taken together, the current study demonstrated that spinal astrocyte and microglial activation may contribute to BmK venom-induced rat pain-related behaviors. Thus, spinal glia may represent novel targets for effective treatment of pain syndrome associated with scorpion envenomation.

In the present study, it was investigated whether the degranulation of mast cells and histamine release were involved in rat pain-related behaviors and edema induced by the venom of scorpion Buthus martensi Karch (BmK) or not. It was found that the obvious degranulation of mast cells could be triggered in rat hindpaw skin by BmK venom. The chronic degranulation of mast cells using compound 48/80 relieved the spontaneous nociceptive responses, the primary thermal and bilateral mechanical hyperalgesia and the rat paw edema, as well as partially reduced c-Fos expression in superficial layers (laminae I-II) of bilateral spinal cord induced by BmK venom. In addition, individual peripheral co-administration of either 100 nmol chlorpheniramine or 100 nmol pyrilamine (histamine H(1) receptor antagonist) or 500 nmol cimetidine (histamine H(2) receptor antagonist) and BmK venom suppressed the spontaneous nociceptive responses, partially the primary thermal and bilateral mechanical hyperalgesia and rat paw edema induced by BmK venom. Thus, these results suggest that the peripheral cellular incidents of mast cells degranulation and histamine release are involved in BmK venom-induced pain-related behaviors and inflammation.

The developmental and pharmacological characteristics of pain responses induced by the experimental scorpion BmK (Buthus martensi Karsch) sting were detailed in this study. Following the unilateral intraplantar injection of BmK venom into rat hind paw, it was found: 1) BmK venom induced an edematogenic response, spontaneous pain and pain hypersensitivity in a dose-dependent manner; 2) the paw edema and flare were induced rapidly and restricted at the injected paw for about 24-48 h; 3) the monophasic tonic spontaneous pain manifested as continuous paw flinching and lifting/licking of the injected paw and lasted for more than 2 h; 4) the detectable thermal hypersensitivity to radiant heat stimuli was just at the injected side for about 72-96 h; 5) the mechanical hypersensitivity to von Frey filaments was evoked surprisingly to be the bilateral and mirror-like for about 2-3 weeks; 6) morphine, indomethacin and bupivacaine could suppress BmK venom-induced pain responses with different intensity and time courses. The results indicated that the experimental BmK sting could evoke the prolonged paw inflammation, tonic spontaneous behaviors, unilateral thermal and bilateral mechanical hypersensitivity. The distinct time development of pain responses induced by experimental BmK sting might be involved in different nervous and/or tissue mechanisms. The experimental BmK sting test thus may be an available tissue injury-induced tonic inflammatory pain model for understanding the mechanisms underlying clinical spontaneous pain, thermal and mirror-imaged bilateral mechanical pain hypersensitivity.