Acupuncture points injection mitigates chronic pain through transient receptor potential V1 in mice

Document Type : Original Article

Authors

1 College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 40402, Taiwan

2 Department of Nuclear Medicine, E-DA Hospital, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan

3 College of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan

4 Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan

Abstract

Objective(s): Tissue injury in peripheral sites can result in long-term potentiation in nociceptive neurons and surrounding glial cells, potentially resulting in the development of chronic inflammatory pain (CIP). Acupoint injection (AI) is similar to Western phototherapy, which injects solutions at specific sites to mitigate chronic pain. AI has shown greater benefits compared with acupuncture. In this study, we examined the therapeutic effect and explored the underlying mechanisms of AI in mice CIP model. 
Materials and Methods: We injected thrice complete Freund’s adjuvant (CFA) into the mouse’s hind paw to induce CIP. 
Results: We found that, after two weeks, CFA injection significantly induced mechanical and thermal hyperalgesia which were attenuated by AI treatment. Transient receptor potential V1 (TRPV1) channels and associated molecules were all increased in CIP in mice dorsal root ganglion (DRG), spinal cord (SC), thalamus, and somatosensory cortex (SSC). The aforementioned molecules were mitigated in AI and Trpv1 knockout mice. Furthermore, Iba1-positive cells (microglial marker) were also potentiated and shared a similar tendency with TRPV1.
Conclusion: These findings suggest that AI can alleviate chronic pain by reducing TRPV1 overexpression in both neuronal and microglial cells. Our results suggest new potential therapeutic targets for AI in chronic pain.

Keywords

References

1. Chung MW, Hsu CY, Chung WK, Lin YN. Effects of dextrose prolotherapy on tendinopathy, fasciopathy, and ligament injuries, fact or myth?: a systematic review and meta-analysis. Medicine 2020; 99:1-8. 
2. Nuhmani S. Injection therapies for patellar tendinopathy. Phys Sportsmed 2020; 48:125-130.
3. Rabago D, Nourani B. Prolotherapy for osteoarthritis and tendinopathy: A descriptive review. Curr Rheumatol Rep 2017; 19:34-41.
4. Reeves KD, Sit RW, Rabago DP. Dextrose prolotherapy: a narrative review of basic science, clinical Research, and best treatment recommendations. Phys Med Rehabil Clin N Am 2016; 27:783-823. 
5. Siadat AH, Isseroff RR. Prolotherapy: potential for the treatment of chronic wounds? Adv Wound Care 2019; 8:160-167.
6. Jensen KT, Rabago DP, Best TM, Patterson JJ, Vanderby R Jr. Early inflammatory response of knee ligaments to prolotherapy in a rat model. J Orthop Res 2008; 26:816-823.
7. Frias B, Merighi A. Capsaicin, nociception and pain. Molecules 2016; 21:797-829.
8. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000; 288:306-313.
9. Kong WL, Peng YY, Peng BW. Modulation of neuroinflammation: role and therapeutic potential of TRPV1 in the neuro-immune axis. Brain Behav Immun 2017; 64:354-366.
10. Lin YW, Chou AIW, Su H, Su KP. Transient receptor potential V1 (TRPV1) modulates the therapeutic effects for comorbidity of pain and depression: the common molecular implication for electroacupuncture and omega-3 polyunsaturated fatty acids. Brain Behav Immun 2020; 89:604-614.
11. Liao HY, Hsieh CL, Huang CP, Lin YW. Electroacupuncture attenuates CFA-induced inflammatory pain by suppressing Nav1.8 through S100B, TRPV1, opioid, and adenosine pathways in mice. Sci Rep 2017; 7:42531-42543. 
12. Obata K, Noguchi K. MAPK activation in nociceptive neurons and pain hypersensitivity. Life Sci 2004; 74:2643-2653. 
13. Sweatt JD. The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 2001; 76:1-10. 
14. Itoh K, Minakawa Y, Kitakoji H. Effect of acupuncture depth on muscle pain. Chin Med 2011; 6:24-28. 
15. Zaringhalam J, Manaheji H, Rastqar A, Zaringhalam M. Reduction of chronic non-specific low back pain: a randomised controlled clinical trial on acupuncture and baclofen. Chin Med 2010; 5:15-21.
16. Wu SY, Chen WH, Hsieh CL, Lin YW. Abundant expression and functional participation of TRPV1 at Zusanli acupoint (ST36) in mice: mechanosensitive TRPV1 as an “acupuncture-responding channel”. BMC Complement Altern Med 2014; 14:96-110.
17. Huang HY, Liao HY, Lin YW. Effects and mechanisms of electroacupuncture on chronic inflammatory pain and depression comorbidity in mice. Evid Based Complement Alternat Med 2020; 4951591:1-10. 
18. Yen CM, Wu TC, Hsieh CL, Huang YW, Lin YW. Distal electroacupuncture at the LI4 acupoint reduces CFA-induced inflammatory pain via the brain TRPV1 signaling pathway. Int J Mol Sci 2019; 20:18-30. 
19. Liao HY, Hsieh CL, Huang CP, Lin YW. Electroacupuncture attenuates induction of inflammatory pain by regulating opioid and adenosine pathways in mice. Sci Rep 2017; 7:1-9.
20. Kumar AM, Venkatesh D, Ravindra S. Electromyography changes in assessment of functional status of muscles in subjects with knee-osteoarthritis undergoing low level laser therapy. Biomedicine 2021; 41:82-87. 
21. Goldman N, Chen M, Fujita T, Xu Q, Peng W, Liu W, et al. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci 2010; 13:883-888. 
22. Torres-Rosas R, Yehia G, Pena G, Mishra P, del Rocio Thompson-Bonilla M, Moreno-Eutimio MA, et al. Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat Med 2014; 20:291-295.
23. Ishikawa S, Suga H, Fukushima M, Yoshida A, Yoshida Y, Sunagawa M, et al. Blood fluidity enhancement by electrical acupuncture stimulation is related to an adrenergic mechanism. J Acupunct Meridian Stud 2012; 5:21-28.
24. Carbone E. Noradrenergic inhibition of presynaptic TRPV1 channels: a new pathway of pain control. J Physiol 2017; 595:2413-2414. 
25. Storozhuk MV, Moroz OF, Zholos AV. Multifunctional TRPV1 ion channels in physiology and pathology with focus on the Brain, vasculature, and some visceral systems. BioMed Res Int 2019; 5806321:1-12. 
26. Zhuang ZY, Xu H, Clapham DE, Ji RR. Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization. J Neurosci 2004; 24:8300-8309. 
27. Inprasit C, Huang YC, Lin YW. Evidence for acupoint catgut embedding treatment and TRPV1 gene deletion increasing weight control in murine model. Int J Mol Med 2020; 45: 779-792.
28. Lottering B, Lin YW. Functional characterization of nociceptive mechanisms involved in fibromyalgia and electroacupuncture. Brain Res 2021; 1755:147260-147272.
29. Inprasit C, Lin YW. TRPV1 responses in the cLobules V, VIa and VII using electroacupuncture treatment for inflammatory hyperalgesia in murine model. Int J Mol Sci 2020; 21:3312-3327.
30. Moreno AM, Aleman F, Catroli GF, Hunt M, Hu M, Dailamy A, et al. Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice. Sci Transl Med 2021; 13:1-29. 
31. Laird JM, Souslova V, Wood JN, Cervero F. Deficits in visceral pain and referred hyperalgesia in Nav1.8 (SNS/ PN3)-null mice. J Neurosci 2002; 22:8352- 8356. 
32. He W, Wang XY, Shi H, Bai WZ, Cheng B, Su YS, et al. Cutaneous neurogenic inflammation in the sensitized acupoints induced by gastric mucosal injury in rats. BMC Complement Alternat Med 2017; 17:141-149.
33. Hou M, Xie JF, Kong XP, Zhang Y, Shao YF, Wang C, et al. Acupoint injection of onabotulinumtoxin A for migraines. Toxins 2015; 7:4442-4454.
34. Ji C, Song F, Huang G, Wang S, Liu H, Liu S, et al. The protective effects of acupoint gel embedding on rats with myocardial ischemia-reperfusion injury. Life Sci 2018; 211:51-62.
35. Liao HY, Hsieh CL, Huang CP, Lin YW. Electroacupuncture attenuates CFA-induced inflammatory pain by suppressing Nav1. 8 through S100B, TRPV1, opioid, and adenosine pathways in mice. Sci Rep 2017; 7:1-13.
Iranian Journal of Basic Medical Sciences
Volume 25, Issue 4
April 2022
Pages 451-459

Files

Share

How to cite

Statistics