The role of CGRP receptor antagonist (CGRP8-37) and Endomorphin-1 combination therapy on neuropathic pain alleviation and expression of Sigma-1 receptors and antioxidants in rats

J Chem Neuroanat. 2020 Jul:106:101771. doi: 10.1016/j.jchemneu.2020.101771. Epub 2020 Feb 21.

Abstract

Background: Spinal cord injury is one of the most common causes of neuropathic pain which is not responsive to common treatments. Owing to the adverse effects of drugs, it seems that the use of Calcitonin Gene-Related Protein (CGRP) receptor antagonist or Morphine and their combination could be an appropriate strategy for pain alleviation.

Method: To achieve the objective, fifty six male Wistar rats were divided into seven groups. CGRP8-37 and Endomorphin-1 alone, and in combinated administration, as bolus and continues dose. Both mechanical and cold allodynia, and mechanical hyperalgesia were evaluated before and also15 and 60 min after injection to indicate the efficacy of the therapies in the acute and chronic circumstances on pain induced by spinal cord compression injury. Sigma-1 receptor experssion, oxidant and antioxidant activity after the seven days of the drug adminestration were evaluated.

Result: The results showed that Endomorphin-1and CGRP8-37 injections were able to reduce neuropathic pain after spinal cord compression injury. Compared to Endomorphin-1, or CGRP8-37 monotherapy, combination therapy did not show more attenuating effects on the pain threshold. Compared to the continous administration of Endomorphin-1 alone, and CGRP8-37 alone, the continous combination therapy did not reduce the pain further. Molecular studies disclosed the increased expression of the Sigma1 receptor, in the spinal cord after administration of Endomorphin-1, and CGRP8-37 alone, as well as combination therapy. Although, an increase in GPx and SOD activity, and decrease in MDA activity was observed in the combination therapy.

Conclusion: Our results demonstrate that either Endomorphin-1 or CGRP receptor antagonist is able to decrease the neuropathic pain after SCI but combination therapy by a CGRP receptor antagonist and Endomorphin-1 did not make any further reduction in pain sensation.

Keywords: CGRP8-37; Combination therapy; Endomorphin-1; Neuropathic pain; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Analgesics, Opioid / therapeutic use*
  • Animals
  • Calcitonin Gene-Related Peptide / pharmacology
  • Calcitonin Gene-Related Peptide / therapeutic use*
  • Calcitonin Gene-Related Peptide Receptor Antagonists / pharmacology
  • Calcitonin Gene-Related Peptide Receptor Antagonists / therapeutic use*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Glutathione Peroxidase / metabolism
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / etiology
  • Hyperalgesia / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Neuralgia / drug therapy*
  • Neuralgia / etiology
  • Neuralgia / metabolism
  • Oligopeptides / pharmacology
  • Oligopeptides / therapeutic use*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Peptide Fragments / pharmacology
  • Peptide Fragments / therapeutic use*
  • Rats
  • Rats, Wistar
  • Receptors, sigma / metabolism*
  • Sigma-1 Receptor
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Spinal Cord Compression / complications
  • Superoxide Dismutase / metabolism
  • Treatment Outcome

Substances

  • Analgesics, Opioid
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Oligopeptides
  • Peptide Fragments
  • Receptors, sigma
  • endomorphin 1
  • calcitonin gene-related peptide (8-37)
  • Malondialdehyde
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Calcitonin Gene-Related Peptide