Abstract
Osteoarthritis currently has no cure. Acupuncture can benefit patients with knee osteoarthritis by providing pain relief, improving joint function and serving as an effective complement to standard care. However, the underlying mechanisms of its effects are still not completely understood. The present study, an investigation of the effectiveness and mechanisms of electroacupuncture (EA) in attenuating osteoarthritis pain in a rat model, is focused on the involvement of 5-hydroxytryptamine 2A/C (5-HT2A/C) receptors, which play an important role in pain modulation at the spinal level. Osteoarthritis was induced under isoflurane anesthesia by a single intraarticular injection of monosodium iodoacetate (3 mg/50 μL/rat) into one hind leg of each rat. EA was given at acupoints GB 30 and ST 36 on days 1–4 after the injection. Vehicle or ketanserin, a 5-HT2A/C receptor antagonist, was given intraperitoneally (1 mg kg−1) or intrathecally (5 μg or 10 μg/10 μL), 30 min before each EA treatment. Assessment of weight-bearing difference between injected and uninjected hind legs was done on days 0, 1–4 and 7. Fos /serotonin and serotonin/Fluorogold double labeling were performed to determine EA activation of serotonergic neurons in the nucleus raphe magnus (NRM) that project to spinal cord. The results showed that EA significantly decreases weight-bearing difference compared to sham EA. Ketanserin pretreatment blocked the analgesic effect of EA but did not influence weight bearing in sham EA control rats. EA also activated serotonergic NRM neurons that project to the spinal cord. These data show that EA inhibits osteoarthritis-induced pain by enhancing spinal 5-HT2A/2C receptor activity.
Highlights
Osteoarthritis, a widespread condition, affects nearly 21 million people in the United States
The aims of the present study were to test whether electroacupuncture (EA) effectively attenuates pain in an osteoarthritis rat model and whether 5-HT2A/C receptors are involved in such attenuation
EA treatment significantly decreased the weight-bearing difference between healthy and inoculated hind legs when compared to sham EA in the iodoacetateinduced osteoarthritis rat model. This suggests that EA treatment significantly relieves spontaneous pain in this model
Summary
Osteoarthritis, a widespread condition, affects nearly 21 million people in the United States. Its prevalence after age 65 is about 60% in men and 70% in women [1]. Its main symptom is chronic pain that causes loss of mobility and often stiffness. Osteoarthritis is irreversible, and currently there is no cure. The purpose of pharmacological treatments is to control pain and reduce functional limitation. Used medications such as non-steroidal anti-inflammatory drugs have serious and even dangerous side effects, including bleeding and perforated ulcers [2, 3]. Cyclooxygenase-2 inhibitors can reduce the gastrointestinal side effects, but these carry an elevated risk for cardiovascular disease, and some have been withdrawn from the market [4].
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