Antinociceptive effects of systemic tanshinone IIA on visceral and somatic persistent nociception and pain hypersensitivity in rats.

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.

Cao FL ，Su XJ ，Wang Y ，Xu M ，Shan L ... -  《-》

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.

Cao FL ，Xu M ，Wang Y ，Gong KR ，Zhang JT ... -  《-》

Antinociceptive effects of intragastric DL-tetrahydropalmatine on visceral and somatic persistent nociception and pain hypersensitivity in rats.

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.

Cao FL ，Shang GW ，Wang Y ，Yang F ，Li CL ，Chen J ... -  《-》

Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.

Inflammatory pain is an important clinical symptom. The levels of extracellular signal-regulated kinases (ERKs) and the levels of cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play important roles in inflammatory pain. Tanshinone IIA (TIIA) is an important component of Danshen, a traditional Chinese medicine that has been commonly used to treat cardiovascular disease. In this study, we investigated the potential anti-inflammatory nociceptive effects of TIIA on complete Freund's adjuvant (CFA)-induced inflammation and inflammatory pain in rats. The effects of TIIA on CFA-induced thermal and mechanical hypersensitivity were investigated using behavioral tests. The levels of ERKs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transient receptor potential vanilloid 1 (TRPV1) in the fifth segment of the lumbar spinal cord (L5) ganglia were detected by Western blot, and the levels of mRNA and protein production of IL1-β, IL-6 and TNF-α were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). In this study, we found that TIIA attenuates the development of CFA-induced mechanical and thermal hypersensitivity. In addition, p-ERK and NF-κB expression levels were inhibited by TIIA, and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced. Finally, we found that the expression level of TRPV1 was significantly decreased after TIIA injection. This study demonstrated that TIIA has significant anti-nociceptive effects in a rat model of CFA-induced inflammatory pain. TIIA can inhibit the activation of ERK signaling pathways and the expression of pro-inflammatory cytokines. These results suggest that TIIA may be a potential anti-inflammatory and anti-nociceptive drug.

Sun S ，Yin Y ，Yin X ，Cao F ，Luo D ，Zhang T ，Li Y ，Ni L ... -  《-》

Antinociceptive effects of systemic paeoniflorin on bee venom-induced various 'phenotypes' of nociception and hypersensitivity.

Yu HY ，Liu MG ，Liu DN ，Shang GW ，Wang Y ，Qi C ，Zhang KP ，Song ZJ ，Chen J ... -  《-》