NMDA antagonist peptide supplementation enhances pain alleviation by adrenal medullary transplants

NasiriNezhad, F. and Sagen, J. (2005) NMDA antagonist peptide supplementation enhances pain alleviation by adrenal medullary transplants. Cell Transplantation, 14 (4). pp. 203-211.

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Abstract

Spinal transplantation of adrenal medullary chromaffin cells has been shown to decrease pain responses in several animal models. Improved potency may be possible by engineering cells to produce greater levels of naturally derived analgesics. As an initial screen for potential candidates, adrenal medullary transplants were evaluated in combination with exogenously administered neuropeptides in rodent pain models. Histogranin is a 15-amino acid peptide that exhibits NMDA receptor antagonist activity. The stable derivative Ser 1histogranin (SHG) can attenuate pain symptoms in some animal models. The formalin model for neurogenic inflammatory pain and the chronic constriction injury (CCI) model for neuropathic pain were used to evaluate the combined effects of chromaffin cell transplantation and intrathecal (IT) SHG injections. Animals were implanted with either adrenal medullary or control striated muscle tissue in the spinal subarachnoid space. For evaluation of formalin responses, animals were pretreated with SHG (0.5, 1.0, 3.0 μg) followed by an intraplantar injection of formalin, and flinching responses were quantified. Pretreatment with SHG had no significant effect on flinching behavior in control animals at lower doses, with incomplete attenuation only at the highest dose. In contrast, 0.5 μg SHG significantly reduced flinching responses in animals with adrenal medullary transplants, and 1.0 μg nearly completely eliminated flinching in these animals in the tonic phase. For evaluation of effects on neuropathic pain, animals received transplants 1 week following CCI, and were tested for thermal and mechanical hyperalgesia and cold allodynia before and following SHG treatment. The addition of low doses of SHG nearly completely eliminated neuropathic pain symptoms in adrenal medullary transplanted animals, while in control transplanted animals only thermal hyperalgesia was attenuated, at the highest dose of SHG. These results suggest that SHG can augment adrenal medullary transplants, and the combination may result in improved effectiveness and range in the treatment of chronic pain syndromes. Copyright © 2005 Cognizant Comm. Corp.

Item Type: Article
Additional Information: cited By 13
Uncontrolled Keywords: analgesic agent; formaldehyde; histogranin; n methyl dextro aspartic acid receptor blocking agent; neuropeptide; unclassified drug, adrenal medulla; allodynia; animal cell; animal model; animal tissue; attenuation; cell transplantation; chromaffin cell; conference paper; controlled study; drug megadose; hyperalgesia; low drug dose; male; muscle transplantation; neuropathic pain; nonhuman; priority journal; rat; skeletal muscle; subarachnoid space, Animalia; Rodentia
Subjects: QV Pharmacology
Divisions: School of Pharmacy > Department of Medicinal Chemistry
Depositing User: Librarian Farzaneh Dini
Date Deposited: 04 May 2019 06:05
Last Modified: 04 May 2019 06:05
URI: http://eprints.iums.ac.ir/id/eprint/12215

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