Abstract
IntroductionDue to side effects of medications used for chronic pain, combination therapy seems to be an appropriate solution for alleviation of chronic pain and reducing the side effects. The role of inhibitory GABA system is well proven in reducing neuropathic pain. Also, special attention has been focused on endogenous morphine (endomorphins) in reducing chronic pain originates from damage to the nervous system. The purpose of this study is to investigate the analgesic effect of simultaneous administration of GABA agonist and endomorphin‐1 on neuropathic pain in rat model of spinal cord injury (SCI). The role of oxidative stress, NR1 subunits of NMDA receptors, and α2 subunits of GABA receptors in the spinal cord has also been investigated.MethodsSpinal cord at level of T6–T8 was compressed. Three weeks after spinal cord injury, muscimol and endomorphin‐1 were injected (intrathecally once a day for 7 days) individually or in combination. Mechanical and cold allodynia, thermal and mechanical hyperalgesia were evaluated before injection and 15 and 60 min after injection. At the end of behavioral experiments, histological and biochemical evaluations were done on prepared spinal cord samples.ResultsIsobologram results showed that combination therapy significantly increased the pain threshold comparing to injection of endomorphin‐1 (EM) or muscimol alone. Histological studies indicated the increased expression of α2 subunits of GABA receptors, and NR1 subunits of NMDA receptors in the spinal cord. The combination therapy also increased the glutathione (GSH) and superoxide dismutase (SOD) level and decreased the malondialdehyde (MDA) levels in the spinal cord.ConclusionSimultaneous administration of muscimol and endomorphine‐1 could be a new candidate for alleviation of pain resulting from spinal cord injury.
Highlights
Due to side effects of medications used for chronic pain, combination therapy seems to be an appropriate solution for alleviation of chronic pain and reducing the side effects
We evaluated the therapeutic effects of endomorphin-1 and muscimol on neuropathic pain threshold in a rat model of spinal cord injury (SCI)
The results of this study indicate that combination therapy with muscimol and endomorphin-1 for seven consecutive days can reduce the pain threshold of animals with SCI compared to the administration of each medication individually
Summary
Due to side effects of medications used for chronic pain, combination therapy seems to be an appropriate solution for alleviation of chronic pain and reducing the side effects. The role of inhibitory GABA system is well proven in reducing neuropathic pain. The purpose of this study is to investigate the analgesic effect of simultaneous administration of GABA agonist and endomorphin-1 on neuropathic pain in rat model of spinal cord injury (SCI). Histological studies indicated the increased expression of α2 subunits of GABA receptors, and NR1 subunits of NMDA receptors in the spinal cord. Conclusion: Simultaneous administration of muscimol and endomorphine-1 could be a new candidate for alleviation of pain resulting from spinal cord injury. GABA B receptor is metabotropic type and coupled to G-proteins This receptor reduces calcium inflow or potassium outflow across the cell via the second messenger or reducing the level of intracellular CAMP; slow excitatory postsynaptic potentials blocked by agonists of this GABA receptor (Watanabe et al, 2002). Muscimol is a GABA A receptor agonist and a local anesthetic extracted from “Amanita muscaria” mushroom. (Johnston, 2014)
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