Levo-tetrahydropalmatine attenuates oxaliplatin-induced mechanical hyperalgesia in mice

Abstract

Common chemotherapeutic agents such as oxaliplatin often cause neuropathic pain during cancer treatment in patients. Such neuropathic pain is difficult to treat and responds poorly to common analgesics, which represents a challenging clinical issue. Corydalis yanhusuo is an old traditional Chinese medicine with demonstrated analgesic efficacy in humans. However, the potential analgesic effect of its active component, levo-tetrahydropalmatine (l-THP), has not been reported in conditions of neuropathic pain. This study found that l-THP (1–4 mg/kg, i.p.) produced a dose-dependent anti-hyperalgesic effect in a mouse model of chemotherapeutic agent oxaliplatin-induced neuropathic pain. In addition, we found that the anti-hyperalgesic effect of l-THP was significantly blocked by a dopamine D1 receptor antagonist SCH23390 (0.02 mg/kg), suggesting a dopamine D1 receptor mechanism. In contrast, l-THP did not significantly alter the general locomotor activity in mice at the dose that produced significant anti-hyperalgesic action. In summary, this study reported that l-THP possesses robust analgesic efficacy in mice with neuropathic pain and may be a useful analgesic in the management of neuropathic pain.

Antinociceptive Profile of Levo-tetrahydropalmatine in Acute and Chronic Pain Mice Models: Role of spinal sigma-1 receptor

“…They also reported that dl-THP pretreatment of the higher dose produce distinct suppression of bee venom or formalin induced persistent nociception. In addition, i.p of l-THP treatment produces a dose-dependent anti-hyperalgesic effect in a mouse model of chemotherapeutic agent oxaliplatin-induced neuropathic pain9. Furthermore, systemic treatment with l-THP exerts remarkable antihyperalgesic effects in a dose dependent manner in a neuropathic pain induced by segmental spinal nerve ligation and inflammatory pain induced by an intraplantar injection of complete Freund’s adjuvant10.…”

“…reported that the analgesic action of i.p treatment with l-THP is mediated by blocking supraspinal dopamine D2 receptors33. Recently, in a chronic pain model such as chemotherapy induced pain model or nerve injury model, i.p treatment with l-THP produced a dose-dependent anti-hyperalgesic effect and this effect was partially blocked by a systemic administration of dopamine D1 receptor antagonist, suggesting a dopamine D1 receptor mechanism910. Therefore, it is possible that the effect of l-THP is mediated by interaction in supraspinal or spinal dopamine receptor and spinal Sig-1R.…”

“…Recently we have revealed that repetitive oral treatments of the extract from CT during the induction phase (day 0–5 after surgery) significantly alleviate chronic constriction injury (CCI)-induced MA, but not TH and reduce increase of spinal pNR1 in rats6. Levo-tetrahydropalmatine (l-THP) is one of active ingredient from Corydalis tuber and has an analgesic effects in several pain7891011. However, although previous reports have reported that l-THP has potential effect for treatment of inflammatory or neuropathic chronic pain, the precise mechanisms underlying the antinociceptive effect of l-THP within the spinal cord has not been established.…”

An Ultra-High Performance Liquid Chromatography with Tandem Mass Spectrometry Method for Determination of 10 Alkaloids in Beagle Dog Plasma after the Oral Administration of the Corydalis yanhusuo W.T. Wang Extract and Yuanhuzhitong Tablets

“…Meanwhile, tetrahydropalmatine is the one alkaloid that has been selected as a phytochemical marker for the quality control of C. yanhusuo in the Chinese Pharmacopoeia [ 1 ]. Tetrahydropalmatine, corydaline, tetrahydrobeberine and berberine have a significant analgesic effect [ 16 , 17 ]. Dehydrocorydaline and coptisine have the effect of anti-inflammatory and anti-coronary heart disease [ 18 ].…”

Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway

“…Clinically, the combination oxycodone and acetaminophen (O&A) is a combined opioid/non-opioid pain reliever which relief the moderate to severe pain [ 26 ]. A recent study has shown that administration of levo -tetrahydropalmatine ( l -THP) [ 27 ] at the dose of 60 mg/kg significantly prevented and/or reversed bone cancer-related pain behaviors, and inhibited tumor cell implantation-induced activation of microglial cells and the increased levels of tumor necrosis factor (TNF)-α and interleukine (IL)-18 [ 18 ]. Our previous studies showed that levo -corydalmine ( l -CDL) ( Figure 1 ), which is a THP’s desmethyl metabolite exhibited better analgesic effects and fewer side effects than l -THP.…”