Acid-sensing ion channel 1a in the central nucleus of the amygdala regulates anxiety-like behaviors in a mouse model of acute pain.

Pain is commonly comorbid with anxiety; however, the neural and molecular mechanisms underlying the comorbid anxiety symptoms in pain (CASP) have not been fully elucidated. In this study, we explored the role of acid-sensing ion channel 1a (ASIC1a), located in GABAergic neurons from the central nucleus of the amygdala (GABACeA), in the regulation of CASP in an acute pain mouse model. We found that the mice displayed significant mechanical pain sensitization and anxiety-like behaviors one day post injection of complete Freud's adjuvant (CFA1D). Electrophysiological recordings from acute brain slices showed that the activity of GABACeA neurons increased in the CFA1D mice compared with that in the saline mice. In addition, chemogenetic inhibition of GABACeA neurons relieved mechanical pain sensitization and anxiety-like behaviors in the CFA1D mice. Interestingly, through pharmacological inhibition and genetic knockdown of ASIC1a in the central nucleus amygdala, we found that downregulation of ASIC1a relieved the hypersensitization of mechanical stimuli and alleviated anxiety-related behaviors, accompanied with reversing the hyperactivity of GABACeA neurons in the CFA 1D mice. In conclusion, our results provide novel insights that ASIC1a in GABACeA neurons regulates anxiety-like behaviors in a mouse model of acute pain.

Sanguinarine Attenuates Neuropathic Pain by Inhibiting P38 MAPK Activated Neuroinflammation in Rat Model.

BACKGROUND: Neuropathic pain seriously affects life quality, and it is urgent to develop novel drugs with high efficacy and few side effects. Sanguinarine (SG) is a natural plant medicine with anti-inflammatory and neuroprotection effects. This study aimed to investigate the effect of SG on chronic constriction injury (CCI)-induced neuropathic pain. MATERIALS AND METHODS: CCI rat model was established and rats were randomly divided into sham group, sham + SG group (6.25 mg/kg), CCI group, CCI + SG group (1.00, 2.50 and 6.25 mg/kg). The mechanical sensitivity and heat hypersensitivity of rats were monitored at different time points. Immunohistochemical, PCR, Western blot and ELISA were used to analyze p-p38 MAPK, NF-κB p65, TNF-α, IL-1ß, and IL-6 levels. RESULTS: The mechanical sensitivity and heat hypersensitivity significantly reduced in rats of CCI group, but significantly increased in rats of CCI+SG group. TNF-α, IL-1ß, and IL-6 levels significantly increased in the spinal cord of CCI rats, but significantly decreased in rats of CCI+SG group. In addition, p38 MAPK activator antagonized beneficial effects of SG on neuropathic pain. Overexpression of p38 MAPK reduced the mechanical sensitivity and heat hypersensitivity, and enhanced NF-κB activity and the expression of inflammatory factors in CCI rats. CONCLUSION: SG alleviates neuropathic pain via suppressing p38MAPK signaling and downregulating the expression of TNF-α, IL-1ß, IL-6 and NF-κB activation. SG may be a potential therapeutic agent to treat neuropathic pain.

The Diagnosis and Therapy of Degenerative Knee Joint Disease: Expert Consensus from the Chinese Pain Medicine Panel.

At present, there are many constantly updated guidelines and consensuses on the diagnosis and treatment of osteoarthritis both at home and abroad. The recommendations established using methods of evidence-based medicine has experienced strict research on controlling bias and promoting reproduction rate. As a result, the previous evidence was reevaluated, and a lot of changes were provoked in the diagnosis and treatment concept of osteoarthritis. However, several methods not recommended by foreign guidelines are still in use in the current clinical practice in China. On the one hand, Chinese experts have not reached extensive consensus on whether it is necessary to make changes according to foreign guidelines. On the other hand, almost all the current relevant guidelines are on osteoarthritis, but the lesions around knee joints which, as a whole, bear the largest weight in human body, cannot be ignored. For this purpose, Chinese Association for the Study of Pain (CASP) organized some leading experts to formulate this Chinese Pain Specialist Consensus on the diagnosis and treatment of degenerative knee osteoarthritis (DKOA) in combination with the guidelines in foreign countries and the expert experience of clinical practice in China. The consensus, which includes the definition, pathophysiology, epidemiology, clinical manifestation, diagnostic criteria, and treatments of DKOA, is intended to be used by first-line doctors, including pain physicians to manage patients with DKOA.