Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Jan 2015
Tanshinone IIA attenuates neuropathic pain via inhibiting glial activation and immune response.
Neuropathic pain, characterized by spontaneous pain, hyperalgesia and allodynia, is a devastating neurological disease that seriously affects patients' quality of life. We have previously shown that tanshinone IIA (TIIA), an important lipophilic component of Danshen, had significant anti-nociceptive effect in somatic and visceral pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA on neuropathic pain and the underlying mechanisms. Therefore, in the present study, by using spinal nerve ligation (SNL) pain model, the antinociceptive and antihyperalgesic effects of TIIA on neuropathic pain were evaluated by intraperitoneal administration in rats. The results indicated that TIIA dose-dependently inhibited SNL-induced mechanical hyperalgesia. As revealed by OX42 levels, TIIA effectively repressed the activation of spinal microglial activation in SNL-induced neuropathic pain. Meanwhile, TIIA also decreased the expressions of inflammatory cytokines TNF-α and IL-1β in the spinal cord. Furthermore, TIIA inhibited oxidative stress by significantly rescuing the superoxide dismutase (SOD) activity and decreasing the malondialdehyde (MDA). Moreover, TIIA depressed SNL-induced MAPKs activation in spinal cord. ⋯ Taken together, our study provides evidence that TIIA inhibited SNL-induced neuropathic pain through depressing microglial activation and immune response by the inhibition of mitogen-activated protein kinases (MAPKs) pathways. Our findings suggest that TIIA might be a promising agent in the treatment of neuropathic pain.
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Pharmacol. Biochem. Behav. · Jan 2015
Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats.
Metabotropic P2Y receptors subfamily consists of eight functional mammalian receptors. Specifically, P2Y1, P2Y6 and P2Y11 receptors have been described in the sensory nervous system, but their participation, at peripheral level, in behavioral pain models is scarcely understood. This study assessed the role of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain. ⋯ Furthermore, the pronociceptive effect of ADP (100nmol/paw) or MRS2365 (10nmol/paw), UDP (300nmol/paw) or PSB0474 (10pmol/paw) and ATP (1000nmol/paw) or NF546 (3nmol/paw) was blocked by the selective P2Y1 (MRS2500, 0.01nmol/paw), P2Y6 (MRS2578, 3nmol/paw), and P2Y11 (NF340, 1nmol/paw) receptor antagonists, respectively. Western blot analysis confirmed the presence of P2Y1 (66kDa), P2Y6 (36kDa) and P2Y11 (75kDa) receptors in dorsal root ganglia (DRG) and sciatic nerve. Results suggest that peripheral activation of P2Y1, P2Y6 and P2Y11 receptors plays a pronociceptive role in formalin-induced pain.
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Pharmacol. Biochem. Behav. · Dec 2014
Antihyperalgesic effect of 5-HT7 receptor activation on the midbrain periaqueductal gray in a rat model of neuropathic pain.
The 5-HT7 receptor is the most recently discovered receptor for 5-hydroxytryptamine (5-HT), and only little is known about the analgesic potential of this receptor. Adenosine triphosphate (ATP) modulates pain transmission by activating P2X/P2Y receptors, in which the P2X3 subtype is an important target for this effect. This study examined the antihyperalgesic effect of the 5-HT7 receptors in the ventrolateral midbrain periaqueductal gray (vlPAG), a crucial site for endogenous pain inhibition. ⋯ Furthermore, the antihyperalgesic effect of the 5-HT7 receptor was partially but significantly blocked by A-317491 pretreatment. These data indicate that the 5-HT7 receptor in the vlPAG exerts an antihyperalgesic effect on rats with neuropathic pain. The 5-HT7 and P2X3 receptors interact in the vlPAG and exhibit an analgesic action through the enhanced function of the endogenous analgesic system.
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Pharmacol. Biochem. Behav. · Nov 2014
Effects of the calcium channel blockers Phα1β and ω-conotoxin MVIIA on capsaicin and acetic acid-induced visceral nociception in mice.
The effects of intrathecal administration of the toxins Phα1β and ω-conotoxin MVIIA were investigated in visceral nociception induced by an intraperitoneal injection of acetic acid and an intracolonic application of capsaicin. The pretreatments for 2h with the toxins reduced the number of writhes or nociceptive behaviors compared with the control mice. Phα1β administration resulted in an Imax of 84±6 and an ID50 of 12 (5-27), and ω-conotoxin MVIIA resulted in an Imax of 82±9 and an ID50 of 11 (4-35) in the contortions induced by the intraperitoneal injection of acetic acid. The administration of Phα1β resulted in an Imax of 64±4 and an ID50 of 18 (9-38), and ω-conotoxin MVIIA resulted in an Imax of 71±9 and an ID50 of 9 (1-83) in the contortions induced by intracolonic capsaicin administration. Phα1β (100/site) or ω-conotoxin MVIIA (30pmol/site) pretreatments caused a reduction in CSF glutamate release in mice intraperitoneally injected with acetic acid or treated with intracolonic capsaicin. The toxin pretreatments reduced the ROS levels induced by intraperitoneal acetic acid injection. Phα1β, but not ω-conotoxin MVIIA, reduced significantly the ROS levels induced by intracolonic capsaicin administration. ⋯ Phα1β is a ω-toxin with high therapeutic index and a broader action on calcium channels. It shows analgesic effect in several rodents' models of pain, including visceral pain, suggesting that this toxin has the potential to be used in clinical setting as a drug in the control of persistent pathological pain.
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Pharmacol. Biochem. Behav. · Nov 2014
Orexin A induced antinociception in the ventral tegmental area involves D1 and D2 receptors in the nucleus accumbens.
Previous studies have shown that there are functional interactions among the lateral hypothalamus (LH), ventral tegmental area (VTA) and the nucleus accumbens (NAc), implicating pain modulation in the central nervous system. It has been shown that the LH-VTA orexinergic projecting neurons play an important role in mediating the suppression of nociception in animal models. However, little is known about the function of intra-VTA orexin receptors and involvement of D1/D2 receptors within the NAc in this antinociception. ⋯ Our findings showed that intra-accumbal SCH-23390 and sulpiride dose-dependently prevented intra-VTA orexin-induced antinociception. Nevertheless, this effect is more potent in animals that received D2 receptor antagonist. It is supposed that orexin A can induce the antinociception through activation of orexinergic receptors which activate the dopaminergic inputs to the NAc in rats.