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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. Conclusion 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.

Previous studies showed that tanshinone IIA (TIIA), an important lipophilic component of Danshen, has been well-established to exhibit various neuroprotective actions in the nervous system. Although we previously reported that TIIA had a significant anti-nociceptive effect in complete Freund's adjuvant (CFA)-induced pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA in animals and the appropriate indications for treatment of clinical pain remain unclear. Therefore, in the present study, by using both somatic and visceral pain models, the antinociceptive and antihyperalgesic effects of TIIA were evaluated by intraperitoneal administration in rats. In the bee venom (BV) test, when compared with saline controls, systemic pre- and post-treatment with TIIA resulted in an apparent antinociception against persistent spontaneous nociception (PSN) and primary heat and mechanical hypersensitivity, while for the mirror-image heat hypersensitivity, only pre-treatment was effective. Moreover, in the formalin test, the antinociception of TIIA was significant for both phases 1 and 2 in the pretreatment groups, but only effective for phase 2 in the post-treatment group. In the acetic acid writhing test, the number of writhes was effectively blocked by both pre- and post-treatment of TIIA. Taken together, these results provide a new line of evidence showing that TIIA is also able to produce analgesia against various 'phenotypes' of nociception and hypersensitivity.

Although tetrahydropalmatine (THP), an alkaloid constituent of plants from the genera Stephania and Corydalis, is known to have analgesic property, the antinociceptive effects of THP have not been well evaluated experimentally and the appropriate indications for treatment of clinical pain remain unclear. In the present study, nociceptive and inflammatory models of both somatic and visceral origins were used to assess the antinociceptive and antihyperalgesic effects of intragastric (i.g.) pretreatment of dl-THP in rats. In the bee venom (BV) test that has been well established experimentally, i.g. pretreatment of three doses of dl-THP (20, 40, 60 mg/kg, body weight) resulted in less stably antinociceptive effect on the BV-induced persistent paw flinches that are known to be processed by spinal nociceptive circuit, however the drug of the two higher doses produced distinct suppression of the BV-induced persistent nociception rated by nociceptive score that reflects both spinal and supraspinal mediation. Similarly, the antinociception of dl-THP (60 mg/kg) was only significant for phase 1 but not for phase 2 of the formalin-induced persistent paw flinches, however, the inhibition was distinct for both phase 1 and phase 2 of the formalin nociceptive score. For the antihyperalgesic effect, in contrast, pretreatment of dl-THP (60 mg/kg) produced significant inhibition of both primary hyperalgesia to either thermal or mechanical stimuli and the mirror-image thermal hyperalgesia identified in the BV test. In the acetic acid writhing test, the number of writhes was completely blocked at the first 5-min interval followed by a sustained suppression in the remaining period of the whole time course comparing to the vehicle control. These data suggest that i.g. pre-administration of dl-THP could more effectively inhibit visceral nociception as well as thermal and mechanical inflammatory pain hypersensitivity (hyperalgesia) than persistent nociception. Moreover, the drug is likely to produce more effectiveness on supraspinally processed nociceptive behaviors than spinally mediated nociceptive behaviors, implicating an action of THP at the supraspinal level.