Moxibustion attenuates neurogenic detrusor overactivity in spinal cord injury rats by inhibiting M2/ATP/P2X3 pathway

PURPOSE Activation of muscarinic receptors located in bladder sensory pathways is generally considered to be the primary contributor for driving the pathogenesis of neurogenic detrusor overactivity following spinal cord injury. The present study is undertaken to examine whether moxibustion improves neurogenic detrusor overactivity via modulating the abnormal muscarinic receptor pathway. MATERIALS AND METHODS Female Sprague-Dawley rats were subjected to spinal cord injury with T9-10 spinal cord transection. Fourteen days later, animals were received moxibustion treatment for one week. Urodynamic parameters and pelvic afferents discharge were measured. Adenosine triphosphate content in the voided cystometry fluid was determined. Expressions of M2, M3, and P2X3 receptors in the bladder mucosa were evaluated. RESULTS Moxibustion treatment prevented the development of detrusor overactivity in SCI rats, with an increase in the intercontraction interval and micturition pressure threshold and a decrease in afferent activity during filling. The expression of M2 was markedly suppressed by moxibustion, accompanied by a reduction in the levels of ATP and P2X3. M2 receptor antagonist methoctramine hemihydrate had similar effects to moxibustion on bladder function and afferent activity, while the M2-preferential agonist oxotremorine methiodide abolished the beneficial effects of moxibustion. CONCLUSION Moxibustion is a potential candidate for treating neurogenic bladder overactivity in a rat model of spinal cord injury, possibly through inhibiting the M2/ATP/P2X3 pathway.

[1]  N. Belluardo,et al.  Anti-inflammatory and antioxidant effects of muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus , 2019, Scientific Reports.

[2]  Hong-ya Zhang,et al.  [Efficacy of the herbal cake-separated moxibustion with new-type moxibustion device on urinary retention after spinal cord injury]. , 2019, Zhongguo zhen jiu = Chinese acupuncture & moxibustion.

[3]  Geetha Manivasagam,et al.  Spinal cord injury: pathophysiology, treatment strategies, associated challenges, and future implications , 2019, Cell and Tissue Research.

[4]  R. Chess-Williams,et al.  Modulation of lower urinary tract smooth muscle contraction and relaxation by the urothelium , 2018, Naunyn-Schmiedeberg's Archives of Pharmacology.

[5]  Seung-June Oh,et al.  Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury , 2018, World Journal of Urology.

[6]  Takahiro Shimizu,et al.  The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice. , 2017, American journal of physiology. Renal physiology.

[7]  L. Jiao,et al.  [Clinical Observation of Heat-sensitive Moxibustion Combined with Kegel Exercise Therapy for Female Stress Urinary Incontinence]. , 2017, Zhen ci yan jiu = Acupuncture research.

[8]  T. Carlsson,et al.  Urothelial acetylcholine involvement in ATP‐induced contractile responses of the rat urinary bladder , 2017, European journal of pharmacology.

[9]  R. van Mastrigt,et al.  Urethane anesthesia in acute lower urinary tract studies in the male rat , 2017, Laboratory animals.

[10]  Yuanbo Fu,et al.  [Impacts on urodynamic parameters and the protein expressions of M2 and M3 receptors of detrusor in the rats of detrusor hyperreflexia treated with ginger-salt-isolated moxibustion at "Shenque" (CV 8)]. , 2017, Zhongguo zhen jiu = Chinese acupuncture & moxibustion.

[11]  J. Roppolo,et al.  Influence of urothelial or suburothelial cholinergic receptors on bladder reflexes in chronic spinal cord injured cats , 2016, Experimental Neurology.

[12]  Chunxia Huang,et al.  Clinical curative effect of fuzi-cake-separated moxibustion for preventing dysuria after operation for lower limb fracture. , 2014, Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan.

[13]  C. Fry,et al.  Regulation of ACh release from guinea pig bladder urothelial cells: potential role in bladder filling sensations , 2014, British journal of pharmacology.

[14]  F. Liang,et al.  [Bibliometrics analysis on researches of illness spectrum for acu-moxibustion therapy and prospect]. , 2014, Zhen ci yan jiu = Acupuncture research.

[15]  C. Fry,et al.  Purinergic and muscarinic modulation of ATP release from the urothelium and its paracrine actions , 2013, American journal of physiology. Renal physiology.

[16]  Michael L Boninger,et al.  Functional priorities, assistive technology, and brain-computer interfaces after spinal cord injury. , 2013, Journal of rehabilitation research and development.

[17]  A. Ford,et al.  Modulation of bladder afferent signals in normal and spinal cord‐injured rats by purinergic P2X3 and P2X2/3 receptors , 2012, BJU international.

[18]  Janice J Eng,et al.  The health and life priorities of individuals with spinal cord injury: a systematic review. , 2012, Journal of neurotrauma.

[19]  H. Yokoyama,et al.  Role of M2 and M3 muscarinic acetylcholine receptor subtypes in activation of bladder afferent pathways in spinal cord injured rats. , 2010, Urology.

[20]  M. Sasamata,et al.  Effect of tamsulosin on bladder blood flow and bladder function in a rat model of bladder over distention/emptying induced bladder overactivity. , 2011, The Journal of urology.

[21]  Hyejung Lee,et al.  The Effectiveness of Moxibustion: An Overview During 10 Years , 2011, Evidence-based complementary and alternative medicine : eCAM.

[22]  E. Burcher,et al.  Porcine Bladder Urothelial, Myofibroblast, and Detrusor Muscle Cells: Characterization and ATP Release , 2011, Front. Pharmacol..

[23]  F. Cruz,et al.  Spinal Cord Injury and Bladder Dysfunction: New Ideas about an Old Problem , 2011, TheScientificWorldJournal.

[24]  W. C. Groat,et al.  Effects of stimulation of muscarinic receptors on bladder afferent nerves in the in vitro bladder–pelvic afferent nerve preparation of the rat , 2010, Brain Research.

[25]  J. S. French,et al.  What do Spinal Cord Injury Consumers Want? A Review of Spinal Cord Injury Consumer Priorities and Neuroprosthesis from the 2008 Neural Interfaces Conference , 2010, Neuromodulation : journal of the International Neuromodulation Society.

[26]  Naoki Yoshimura,et al.  Changes in afferent activity after spinal cord injury , 2010, Neurourology and urodynamics.

[27]  M. Chancellor,et al.  Differential roles of M2 and M3 muscarinic receptor subtypes in modulation of bladder afferent activity in rats. , 2008, Urology.

[28]  M. Michel,et al.  Basic mechanisms of urgency: preclinical and clinical evidence. , 2009, European urology.

[29]  O. Yamaguchi,et al.  Expression of P2X3 purinoceptors in suburothelial myofibroblasts of the normal human urinary bladder , 2009, International journal of urology : official journal of the Japanese Urological Association.

[30]  Cheng-mei Liu,et al.  [Clinical observation on moxibustion combined with intermittent urethral catheterization for treatment of neurogenic vesical dysfunction]. , 2009, Zhongguo zhen jiu = Chinese acupuncture & moxibustion.

[31]  W. D. de Groat,et al.  Activation of Muscarinic Receptors in Rat Bladder Sensory Pathways Alters Reflex Bladder Activity , 2008, The Journal of Neuroscience.

[32]  W. D. de Groat,et al.  Heterogeneity of muscarinic receptor-mediated Ca 2 (cid:1) responses in cultured urothelial cells from rat , 2008 .

[33]  P. Abrams,et al.  Muscarinic receptor antagonists for overactive bladder , 2007, BJU international.

[34]  W. Jung,et al.  Effects of moxibustion on the recovery of post-stroke urinary symptoms. , 2007, The American journal of Chinese medicine.

[35]  Linpeng Wang,et al.  [Randomized controlled study on ginger-salt-partitioned moxibustion at shenque (CV 8) on urination disorders poststroke]. , 2006, Zhongguo zhen jiu = Chinese acupuncture & moxibustion.

[36]  Naoki Yoshimura,et al.  Mechanisms underlying the recovery of lower urinary tract function following spinal cord injury. , 2006, Progress in brain research.

[37]  G. Burnstock,et al.  Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis. , 2004, American journal of physiology. Renal physiology.

[38]  R. Mastrigt,et al.  Afferent bladder nerve activity in the rat: a mechanism for starting and stopping voiding contractions , 2004, Urological Research.

[39]  M. Pontari,et al.  The M2 muscarinic receptor mediates in vitro bladder contractions from patients with neurogenic bladder dysfunction. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[40]  Hitoshi Iwashita,et al.  Management of detrusor dysfunction in the elderly: changes in acetylcholine and adenosine triphosphate release during aging. , 2004, Urology.

[41]  Yan Sun,et al.  Up-regulation of P2X3 receptor during stretch of bladder urothelial cells from patients with interstitial cystitis. , 2004, The Journal of urology.

[42]  M. Knuepfer Muscarinic Cholinergic and β-Adrenergic Contribution to Hindquarters Vasodilation and Cardiac Responses to Cocaine , 2003, Journal of Pharmacology and Experimental Therapeutics.

[43]  R. Chess-Williams,et al.  Muscarinic receptor subtypes and management of the overactive bladder. , 2002, Urology.

[44]  R. Chess-Williams,et al.  The minor population of M3-receptors mediate contraction of human detrusor muscle in vitro. , 2001, Journal of autonomic pharmacology.

[45]  Geoffrey Burnstock,et al.  Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X 3-deficient mice , 2000, Nature.

[46]  R. Eglen,et al.  Muscarinic receptor subtypes modulating smooth muscle contractility in the urinary bladder. , 1999, Life sciences.

[47]  S. Lindström,et al.  The C fibre reflex of the cat urinary bladder , 1998, The Journal of physiology.

[48]  G. Gabella,et al.  Distribution of afferent axons in the bladder of rats , 1998, Journal of neurocytology.

[49]  W. C. Groat,et al.  Plasticity of Na+ Channels in Afferent Neurones Innervating Rat Urinary Bladder Following Spinal Cord Injury , 1997, The Journal of physiology.

[50]  M. Ruggieri,et al.  Muscarinic acetylcholine receptor subtypes mediating urinary bladder contractility and coupling to GTP binding proteins. , 1995, The Journal of pharmacology and experimental therapeutics.

[51]  W. C. Groat,et al.  Effect of capsaicin on micturition and associated reflexes in chronic spinal rats , 1995, Brain Research.

[52]  M. Cynader,et al.  Muscarinic receptor M1 and M2 subtypes in the human eye: QNB, pirenzipine, oxotremorine, and AFDX-116 in vitro autoradiography. , 1994, The British journal of ophthalmology.

[53]  M Kawatani,et al.  Mechanisms underlying the recovery of urinary bladder function following spinal cord injury. , 1990, Journal of the autonomic nervous system.

[54]  D. Cockayne,et al.  Urinary bladder hypore ̄ exia and reduced pain-related behaviour in P 2 X 3-de ® cient mice , 2022 .