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. 2011:2011:619650.
doi: 10.1093/ecam/neq016. Epub 2011 Jan 9.

Serotonin Receptor 2A/C Is Involved in Electroacupuncture Inhibition of Pain in an Osteoarthritis Rat Model

Aihui Li  1 , Yu Zhang, Lixing Lao, Jiajia Xin, Ke Ren, Brian M Berman, Rui-Xin Zhang
Affiliations

Serotonin Receptor 2A/C Is Involved in Electroacupuncture Inhibition of Pain in an Osteoarthritis Rat Model

Aihui Li et al. Evid Based Complement Alternat Med. 2011.

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.

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Figures

Figure 1
Figure 1
Effect of a unilateral intra-articular injection of monosodium iodoacetate (3 mg/50 μL/rat) on the weight-bearing ability of hind legs (n = 8). Note that iodoacetate-injected rats bore significantly less weight on the ipsilateral hind limb than did saline-injected rats. Abscissas: the time points from the 1st to the 7th day after iodoacetate; ordinate: body weight difference. ***P < .001 versus saline.
Figure 2
Figure 2
Effect of EA and a systemic injection of ketanserin on weight bearing in rats with osteoarthritis. EA significantly decreased weight-bearing differences compared to sham EA on days 3–7 after iodoacetate. Ketanserin pretreatment blocked the analgesic effect of EA but did not influence weight bearing in sham EA control rats. *P < .05, **P < .01, ***P < .001 versus sham + vehicle; # P < .01, & P < .05 versus EA + ketanserin.
Figure 3
Figure 3
Effect of an i.t. ketanserin injection on EA analgesia. Ketanserin at 10 μg pretreatment significantly blocked the analgesic effect of EA on days 2–7 after iodoacetate. There is no significant difference between the 5 μg and vehicle groups. *P < .05, **P < .01, ***P < .001 versus vehicle control.
Figure 4
Figure 4
Co-localization of Fos and 5-HT in the nucleus raphe magnus. (a) The 5-HT-immunoreactive neurons; (b) Fos-immunoreactive profiles; (c) Merged graphs of (a) and (b). Arrows indicate double-labeled 5-HT/Fos neurons (yellow). Arrow heads point to single-labeled neurons.
Figure 5
Figure 5
Representative photograph showing the co-localization of serotonin and Fluorogold in the nucleus raphe magnus. (a) The 5-HT-immunoreactive neurons; (b) Fluorogold-labeled neurons projecting to the spinal cord; (c) Merged graphs of (a) and (b). Arrows indicate double-labeled 5-HT/Fluorogold neurons (yellow).
Figure 6
Figure 6
A schematic illustration of the mechanisms of EA inhibition of pain.
See this image and copyright information in PMC

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