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An increase in spinal cord noradrenaline is a major contributor to the antihyperalgesic effect of antidepressants after peripheral nerve injury in the rat.
Pain. 2012 May; 153(5):990-997.PAIN

Abstract

Antidepressants are often used for the treatment of neuropathic pain. Clinical studies suggest that the efficacy of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs) for neuropathic pain is greater than that of selective 5-HT reuptake inhibitors (SSRIs). In the present study, we determined the efficacy and mechanisms involved in the antihyperalgesic effects of milnacipran, an SNRI, compared with paroxetine, an SSRI, and maprotiline, a selective NA reuptake inhibitor, using a rat model of neuropathic pain. Male Sprague-Dawley rats underwent spinal nerve ligation (SNL), and the withdrawal threshold to paw pressure was measured. Intraperitoneal injection of milnacipran (3-30mg/kg) produced a dose-dependent antihyperalgesic effect. The effect was reversed by intrathecal injection of the α(2)-adrenoceptor antagonist idazoxan (30μg), but not by various 5-HT receptor antagonists. Paroxetine produced an antihyperalgesic effect only at the highest dose tested (10mg/kg). This effect was reversed by intrathecal injection of both idazoxan and ondansetron (30μg), a 5-HT3 receptor antagonist. Maprotiline produced an antihyperalgesic effect (10 and 30mg/kg), and the effect was reversed by intrathecal idazoxan. In microdialysis studies, NA and 5-HT concentrations in the spinal dorsal horn were increased after injection of either milnacipran or paroxetine, and only NA was increased after maprotiline. Furthermore, the NA content in the spinal cord of SNL rats was greater than that in normal animals. These findings suggest that an increase in NA in the spinal cord plays an important role in the antihyperalgesic effects of not only NA reuptake inhibitors but also SSRIs.

Authors+Show Affiliations

Department of Anesthesiology, Gunma University Graduate School of Medicine, Gunma, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22424692

Citation

Nakajima, Kunie, et al. "An Increase in Spinal Cord Noradrenaline Is a Major Contributor to the Antihyperalgesic Effect of Antidepressants After Peripheral Nerve Injury in the Rat." Pain, vol. 153, no. 5, 2012, pp. 990-997.
Nakajima K, Obata H, Iriuchijima N, et al. An increase in spinal cord noradrenaline is a major contributor to the antihyperalgesic effect of antidepressants after peripheral nerve injury in the rat. Pain. 2012;153(5):990-997.
Nakajima, K., Obata, H., Iriuchijima, N., & Saito, S. (2012). An increase in spinal cord noradrenaline is a major contributor to the antihyperalgesic effect of antidepressants after peripheral nerve injury in the rat. Pain, 153(5), 990-997. https://doi.org/10.1016/j.pain.2012.01.029
Nakajima K, et al. An Increase in Spinal Cord Noradrenaline Is a Major Contributor to the Antihyperalgesic Effect of Antidepressants After Peripheral Nerve Injury in the Rat. Pain. 2012;153(5):990-997. PubMed PMID: 22424692.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An increase in spinal cord noradrenaline is a major contributor to the antihyperalgesic effect of antidepressants after peripheral nerve injury in the rat. AU - Nakajima,Kunie, AU - Obata,Hideaki, AU - Iriuchijima,Nobuhisa, AU - Saito,Shigeru, Y1 - 2012/03/15/ PY - 2011/03/02/received PY - 2012/01/13/revised PY - 2012/01/27/accepted PY - 2012/3/20/entrez PY - 2012/3/20/pubmed PY - 2012/8/14/medline SP - 990 EP - 997 JF - Pain JO - Pain VL - 153 IS - 5 N2 - Antidepressants are often used for the treatment of neuropathic pain. Clinical studies suggest that the efficacy of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs) for neuropathic pain is greater than that of selective 5-HT reuptake inhibitors (SSRIs). In the present study, we determined the efficacy and mechanisms involved in the antihyperalgesic effects of milnacipran, an SNRI, compared with paroxetine, an SSRI, and maprotiline, a selective NA reuptake inhibitor, using a rat model of neuropathic pain. Male Sprague-Dawley rats underwent spinal nerve ligation (SNL), and the withdrawal threshold to paw pressure was measured. Intraperitoneal injection of milnacipran (3-30mg/kg) produced a dose-dependent antihyperalgesic effect. The effect was reversed by intrathecal injection of the α(2)-adrenoceptor antagonist idazoxan (30μg), but not by various 5-HT receptor antagonists. Paroxetine produced an antihyperalgesic effect only at the highest dose tested (10mg/kg). This effect was reversed by intrathecal injection of both idazoxan and ondansetron (30μg), a 5-HT3 receptor antagonist. Maprotiline produced an antihyperalgesic effect (10 and 30mg/kg), and the effect was reversed by intrathecal idazoxan. In microdialysis studies, NA and 5-HT concentrations in the spinal dorsal horn were increased after injection of either milnacipran or paroxetine, and only NA was increased after maprotiline. Furthermore, the NA content in the spinal cord of SNL rats was greater than that in normal animals. These findings suggest that an increase in NA in the spinal cord plays an important role in the antihyperalgesic effects of not only NA reuptake inhibitors but also SSRIs. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/22424692/An_increase_in_spinal_cord_noradrenaline_is_a_major_contributor_to_the_antihyperalgesic_effect_of_antidepressants_after_peripheral_nerve_injury_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/00006396-201205000-00012 DB - PRIME DP - Unbound Medicine ER -