The Effect of Intrathecal Administration of Muscimol on Modulation of Neuropathic Pain Symptoms Resulting from Spinal Cord Injury; an Experimental Study
Archives of Academic Emergency Medicine,
Vol. 2 No. 4 (2014),
AbstractIntroduction:Â Neuropathic pain can be very difficult to treat and it is one of the important medical challenging about pain treatments. Muscimol as a new agonist of gamma-Aminobutyric acid receptor type A (GABAA) have been introduced for pain management. Thus, the present study was performed to evaluate the pain alleviating effect of intrathecal injection of different doses of muscimol as GABAAÂ receptor agonist in spinal cord injury (SCI) model of neuropathic pain.Â Methods:Â In the present experimental study male Wistar rats were treated by muscimol 0.01, 0.1 or 1 Âµg/10ul, intrathecally (i.t.) three weeks after induction of spinal cord injury using compression injury model. Neuropathic pain symptoms were assessed at before treatment, 15 minutes, one hour and three hours after muscimol administration. The time of peak effect and optimum dosage was assessed by repeated measures analysis of variance and analysis of covariance, respectively.Â Results: Muscimol with the dose of 0.01 Âµg in 15 minutes caused to improve the thermal hyperalgesia (df: 24, 5; F= 6.6; p<0.001), mechanical hyperalgesia (df: 24, 5; F= 7.8; p<0.001), cold allodynia (df: 24, 5; F= 6.96; p<0.001), and mechanical allodynia (df: 24, 5; F= 15.7; p<0.001). The effect of doses of 0.1 Âµg and 1 Âµg were also significant. In addition, the efficacy of different doses of muscimol didn't have difference on thermal hyperalgesia (df: 24, 5; F= 1.52; p= 0.24), mechanical hyperalgesia (df: 24, 5; F= 0.3; p= -0.75), cold allodynia (df: 24, 5; F= 0.8; p= -0.56), and mechanical allodynia (df: 24, 5; F= 1.75; p= 0.86).Â Conclusion:Â The finding of the present study revealed that using muscimol with doses of 0.01Âµg, 0.1Âµg, and 1 Âµg reduces the symptoms of neuropathic pain. Also the effect of GABAAÂ agonist is short term and its effectiveness gradually decreases by time.
- Neuropathic pain
- GABAA receptor agonists
- pain management
How to Cite
Mann R, Schaefer C, Sadosky A, et al. Burden of spinal cord injury-related neuropathic pain in the United States: retrospective chart review and cross-sectional survey. Spinal Cord. 2013;51(7):564-70.
Wolfe MD, Oâ€™Connor AB. Management of Neuropathic Pain in Hospitalized Patients. Hosp Med Clinics. 2013;2(4):e587-e602.
Schug SA. Drug synergy and therapeutic combinations. Neuropathic Pain: Causes, Management and Understanding. United State: LANGE; 2013. p. 290.
Wiffen PJ, Derry S, Moore RA, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia-an overview of Cochrane reviews. Cochrane Database Syst Rev. 2013;11:CD010567.
Moore RA, Wiffen PJ, Derry S, Toelle T, Rice AS. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Lib. 2014;16(3):CD007938.
McNicol ED, Midbari A, Eisenberg E. Opioids for neuropathic pain. status and date: Edited (no change to conclusions), published in. 2013;8(9):CD006146.
Hayek SM, Hanes MC. Intrathecal Therapy for Chronic Pain: Current Trends and Future Needs. Curr Pain Headache Rep. 2014;18(1):1-9.
Kumar A, Maitra S, Khanna P, Baidya D. Clonidine for management of chronic pain: A brief review of the current evidences. Saudi Journal of Anaesthesia. 2014;8(1):92-6.
Sindou M, Georgoulis G, Mertens P. Intrathecal Baclofen Therapy. Neurosurgery for Spasticity: Springer; 2014. p. 69-101.
Karanikolas M, Aretha D, Tsolakis I, et al. Optimized perioperative analgesia reduces chronic phantom limb pain intensity, prevalence, and frequency: a prospective, randomized, clinical trial. Anesthesiology. 2011;114(5):1144-54.
Andreae M, Andreae D. Regional anaesthesia to prevent chronic pain after surgery: a Cochrane systematic review and meta-analysis. Br J Anaesth. 2013;111(5):711-20.
Giuggioli D, Sebastiani M, Ferri C. Phantom limb pain in patients with severe cryoglobulinemic vasculitis: Usefulness of long-term pregabalin treatment. J Musculoskelet Pain. 2012;20(4):306-9.
Ruan X. Novel epidural baclofen infusion trial for intractable spasticity with long-term follow-up observation and a focused review of the literature. J Pain Relief. 2013;2:121-7.
Pope JE, Deer TR, Kramer J. A systematic review: current and future directions of dorsal root ganglion therapeutics to treat chronic pain. Pain Med. 2013;14(10):1477-96.
Yowtak J, Wang J, Kim HY, Lu Y, Chung K, Chung JM. Effect of antioxidant treatment on spinal GABA neurons in a neuropathic pain model in the mouse. Pain. 2013;154(11):2469-76.
Ghoshal N, Vijayan RSK. Pharmacophore models for GABAA modulators: implications in CNS drug discovery. Expert Opin Drug Discov. 2010;5(5):441-60.
Munro G, Erichsen HK, Rae MG, Mirza NR. A question of balanceâ€“Positive versus negative allosteric modulation of GABAA receptor subtypes as a driver of analgesic efficacy in rat models of inflammatory and neuropathic pain. Neuropharmacology. 2011;61(1):121-32.
Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983;16(2):109-10.
Hama A, Sagen J. Behavioral characterization and effect of clinical drugs in a rat model of pain following spinal cord compression. Brain Res. 2007;1185:117-28.
Xu F, Li T, Zhang B. An improved method for protecting and fixing the lumbar catheters placed in the spinal subarachnoid space of rats. J Neurosci Methods. 2009;183(2):114-8.
Chaplan S, Bach F, Pogrel J, Chung J, Yaksh T. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994;53(1):55-63.
Santos-Nogueira E, Redondo Castro E, Mancuso R, Navarro X. Randall-Selitto test: a new approach for the detection of neuropathic pain after spinal cord injury. J Neurotrauma. 2012;29(5):898-904.
Yoon C, Young Wook Y, Heung Sik N, Sun Ho K, Jin Mo C. Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain. 1994;59(3):369-76.
Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988;32(1):77-88.
Peyron R, Faillenot I, Pomares F, Le Bars D, Garciaâ€Larrea L, Laurent B. Mechanical allodynia in neuropathic pain. Where are the brain representations located? A positron emission tomography (PET) study. European Journal of Pain. 2013;17(9):1327-37.
Hulsebosch CE, Hains BC, Crown ED, Carlton SM. Mechanisms of chronic central neuropathic pain after spinal cord injury. Brain res rev. 2009;60(1):202-13.
Finnerup NB, Baastrup C, Jensen TS. Neuropathic pain following spinal cord injury pain: mechanisms and treatment. Scand J Pain. 2009;1:S3-S11.
Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010;9(8):807-19.
Finnerup NB, Baastrup C. Spinal cord injury pain: mechanisms and management. Curr Pain Headache Rep. 2012;16(3):207-16.
Bareiss SK, Gwaltney M, Hernandez K, Lee T, Brewer KL. Excitotoxic spinal cord injury induced dysesthesias are associated with enhanced intrinsic growth of sensory neurons. Neurosci Lett. 2013;542:113-7.
Zhang N, Yin Y, Xu S-J, Wu Y-P, Chen W-S. Inflammation & apoptosis in spinal cord injury. Indian J Med Res. 2012;135(3):287-96.
Dâ€™Angelo R, Morreale A, Donadio V, et al. Neuropathic pain following spinal cord injury: what we know about mechanisms, assessment and management. Eur Rev Med Pharmacol Sci. 2013;17(23):3257-61.
Cadotte DW, Bosma R, Mikulis D, et al. Plasticity of the injured human spinal cord: insights revealed by spinal cord functional MRI. PLoS One. 2012;7(9):e45560.
Ultenius C, Song Z, Lin P, Meyerson BA, Linderoth B. Spinal GABAergic mechanisms in the effects of spinal cord stimulation in a rodent model of neuropathic pain: is GABA synthesis involved? Neuromodulation: Technology at the Neural Interface. 2013;16(2):114-20.
Chai T, Bruel BM, Nouri KH, Driver LC. Complications after intrathecal drug delivery due to the underlying malignancy in two patients with intractable cancer pain. Pain physician. 2013;16:E107-11.
Williams BS, Wong D, Amin S. Case scenario: self-extraction of intrathecal pump medication with a concomitant intrathecal granulomatous mass. Anesthesiology. 2011;114(2):424-30.
Naik AK, Latham JR, Obradovic A, Jevtovic-Todorovic V. Dorsal root ganglion application of muscimol prevents hyperalgesia and stimulates myelin protein expression after sciatic nerve injury in rats. Anesth Analg. 2012;114(3):674-82.
Naik A, Pathirathna S, Jevtovic-Todorovic V. GABAA receptor modulation in dorsal root ganglia in vivo affects chronic pain after nerve injury. Neuroscience. 2008;154(4):1539-53.
Baba H, Ji R-R, Kohno T, et al. Removal of GABAergic inhibition facilitates polysynaptic A fiber-mediated excitatory transmission to the superficial spinal dorsal horn. Mol Cell Neurosci. 2003;24(3):818-30.
Miletic G, Draganic P, Pankratz MT, Miletic V. Muscimol prevents long-lasting potentiation of dorsal horn field potentials in rats with chronic constriction injury exhibiting decreased levels of the GABA transporter GAT-1. Pain. 2003;105(1):347-53.
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