Dataset Information

Electroacupuncture Potentiates Cannabinoid Receptor-Mediated Descending Inhibitory Control in a Mouse Model of Knee Osteoarthritis.

ABSTRACT: Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA) is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC) function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA). EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG) level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG) can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG)-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.

SUBMITTER: Yuan XC

PROVIDER: S-EPMC5897736 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Electroacupuncture Potentiates Cannabinoid Receptor-Mediated Descending Inhibitory Control in a Mouse Model of Knee Osteoarthritis.

Yuan Xiao-Cui XC Zhu Bing B Jing Xiang-Hong XH Xiong Li-Ze LZ Wu Cai-Hua CH Gao Fang F Li Hong-Ping HP Xiang Hong-Chun HC Zhu He H Zhou Bin B He Wei W Lin Chuan-You CY Pan Hui-Lin HL Wang Qiang Q Li Man M

Frontiers in molecular neuroscience 20180406

Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA) is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC) function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control a ...[more]

PMID: 29681797

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Project description:Background:Neuroplastic changes in nociceptive pathways contribute to severity of symptoms in knee osteoarthritis (KOA). A new look at neuroplastic changes management includes modulation of the primary motor cortex by transcranial direct current stimulation (tDCS). Objectives:We investigated whether tDCS combined with intramuscular electrical stimulation (EIMS) would be more efficacious than a sham (s) intervention (s-tDCS/s-EIMS) or a single active(a)-tDCS/s-EIMS intervention and/or s-tDCS/a-EIMS in the following domains: pain measures (visual analog scale [VAS] score and descending pain modulatory system [DPMS], and outcomes, and analgesic use, disability, and pain pressure threshold (PPT) for secondary outcomes. Registration:The trial is registered in Clinicaltrials.gov: NCT01747070. Methods:Sixty women with KOA, aged 50-75 years old, randomly received five sessions of one of the four interventions (a-tDCS/a-EIMS, s-tDCS/s-EIMS, a-tDCS/s-EIMS, and s-tDCS/a-EIMS). tDCS was applied over the primary motor cortex (M1), for 30 minutes at 2 mA and the EIMS paraspinal of L1-S2. Results:A generalized estimating equation model revealed the main effect of the a-tDCS/a-EIMS in the VAS pain scores at end treatment compared with the other three groups (P<0.0001). There existed a significant effect of time and a significant interaction between group and time (P<0.01 for both). The delta-(?) pain score on VAS in the a-tDCS/a-EIMS group was -3.59, 95% CI: -4.10 to -2.63. The (?) pain scores on VAS in the other three groups were: a-tDCS/s-EIMS=-2.13, 95% CI: -2.48 to -1.64; s-tDCS/a-EIMS=-2.25, 95% CI: -2.59 to -1.68; s-tDCS/s-EIMS MR =-1.77, 95% CI: -2.08 to -1.38. The a-tDCS/a-EIMS led to better effect in DPMS, PPT, analgesic use, and disability related to pain. Conclusion:This study provides additional evidence regarding additive clinical effects to improve pain measures and descending pain inhibitory controls when the neuromodulation of the primary motor cortex with tDCS is combined with a bottom-up modulation with EIMS in KOA. Also, it improved the ability to walk due to reduced pain and reduced analgesic use.

Project description:BackgroundKnee osteoarthritis (KOA) is a common degenerative joint disorder that affects 250 million people globally. KOA can lead to disability and is often associated with cardiovascular disease, poor quality of life, and mortality. The most common treatment for KOA is non-steroidal anti-inflammatory drug administration. However, the analgesic effect is limited and often accompanied by multiple side effects. Hence, many KOA patients opt for complementary and alternative medicine. Acupuncture is one of the most popular complementary treatments with great analgesic effect and minimal side effect. Electroacupuncture (EA) and laser acupuncture (LA) have been known to reduce pain in KOA patients. However, to date, no study has assessed the benefits of combining these two therapies.MethodsFifty participants diagnosed with KOA, aged 50 years or older, and with consistent knee pain for more than 3 months were recruited and randomly assigned to the treatment group (EA plus LA) or control group (EA plus sham LA without laser output). All subjects in the treatment group will undergo a combined EA and LA treatment thrice a week for 4 weeks. The acupuncture will be performed on GB33, GB34, SP9, SP10, and ST36 sites. The treatment group will receive acupuncture with a transcutaneous electrical nerve stimulator at GB33, GB34, SP9, and SP10 sites and with LA at EX-LE5, ST35, and BL40 sites. The subjects in the control group will undergo the same treatment modality as the treatment group, except these subjects will not be exposed to laser output. Outcome measurements will include visual analog scale, Western Ontario McMaster Universities Osteoarthritis Index, Knee injury and osteoarthritis outcome, body composition analysis, knee range of motion, quadriceps muscle stiffness, one-leg standing with eyes open test, and the 30-s chair stand test before and after 4 weeks of intervention.ObjectivesThis protocol aims to investigate the combined effect of EA and LA in KOA patients.

Project description:Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA and protein expression in an OA pain model. The expression of CB2 receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB2 receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data provide new clinically relevant evidence that joint damage and spinal CB2 receptor expression are correlated combined with converging pre-clinical evidence that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation of chronic OA pain. These findings suggest that targeting CB2 receptors may have therapeutic potential for treating OA pain.

Dataset Information

Electroacupuncture Potentiates Cannabinoid Receptor-Mediated Descending Inhibitory Control in a Mouse Model of Knee Osteoarthritis.

Publications

Electroacupuncture Potentiates Cannabinoid Receptor-Mediated Descending Inhibitory Control in a Mouse Model of Knee Osteoarthritis.

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