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TRPA1, NMDA receptors and nitric oxide mediate mechanical hyperalgesia induced by local injection of magnesium sulfate into the rat hind paw.
Physiol Behav. 2015 Feb; 139:267-73.PB

Abstract

Previous studies have shown that while magnesium, an antagonist of the glutamate subtype of N-methyl-D-aspartate receptors, possesses analgesic properties, it can induce writhing in rodents. The aim of this study was to determine the effect and mechanism of action of local (intraplantar) administration of magnesium sulfate (MS) on the paw withdrawal threshold (PWT) to mechanical stimuli. The PWT was evaluated by the electronic von Frey test in male Wistar rats. Tested drugs were either co-administered intraplantarly (i.pl.) with MS or given into the contralateral paw to exclude systemic effects. MS at doses of 0.5, 1.5, 3 and 6.2 mg/paw (i.pl.) induced a statistically significant (as compared to 0.9% NaCl) and dose-dependent mechanical hyperalgesia. Only isotonic MS (250 mmol/l or 6.2% or 6.2 mg/paw) induced mechanical hyperalgesia that lasted at least six hours. Isotonic MS-induced mechanical hyperalgesia was reduced in a dose-dependent manner by co-injection of camphor, a non-selective TRPA1 antagonist (0.3, 1 and 2.5 μg/paw), MK-801, a NMDA receptor antagonist (0.001, 0.025 and 0.1 μg/paw), L-NAME, a non-selective nitric oxide (NO) synthase inhibitor (20, 50 and 100 μg/paw), ARL 17477, a selective neuronal NOS inhibitor (5.7 and 17 μg/paw), SMT, a selective inducible NOS inhibitor (1 and 2.78 μg/paw), and methylene blue, a guanylate cyclase inhibitor (5, 20 and 125 μg/paw). Drugs injected into the contralateral hind paw did not produce significant effects. These results suggest that an i.pl. injection of MS produces local peripheral mechanical hyperalgesia via activation of peripheral TRPA1 and NMDA receptors and peripheral production of NO.

Authors+Show Affiliations

Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: srebrodragana1@gmail.com.Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Pub Type(s)

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

Language

eng

PubMed ID

25449407

Citation

Srebro, Dragana P., et al. "TRPA1, NMDA Receptors and Nitric Oxide Mediate Mechanical Hyperalgesia Induced By Local Injection of Magnesium Sulfate Into the Rat Hind Paw." Physiology & Behavior, vol. 139, 2015, pp. 267-73.
Srebro DP, Vučković SM, Savić Vujović KR, et al. TRPA1, NMDA receptors and nitric oxide mediate mechanical hyperalgesia induced by local injection of magnesium sulfate into the rat hind paw. Physiol Behav. 2015;139:267-73.
Srebro, D. P., Vučković, S. M., Savić Vujović, K. R., & Prostran, M. Š. (2015). TRPA1, NMDA receptors and nitric oxide mediate mechanical hyperalgesia induced by local injection of magnesium sulfate into the rat hind paw. Physiology & Behavior, 139, 267-73. https://doi.org/10.1016/j.physbeh.2014.11.042
Srebro DP, et al. TRPA1, NMDA Receptors and Nitric Oxide Mediate Mechanical Hyperalgesia Induced By Local Injection of Magnesium Sulfate Into the Rat Hind Paw. Physiol Behav. 2015;139:267-73. PubMed PMID: 25449407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRPA1, NMDA receptors and nitric oxide mediate mechanical hyperalgesia induced by local injection of magnesium sulfate into the rat hind paw. AU - Srebro,Dragana P, AU - Vučković,Sonja M, AU - Savić Vujović,Katarina R, AU - Prostran,Milica Š, Y1 - 2014/11/18/ PY - 2014/06/03/received PY - 2014/11/10/revised PY - 2014/11/12/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/9/1/medline KW - Magnesium sulfate KW - NMDA KW - Nitric oxide KW - Peripheral mechanical hyperalgesia KW - TRPA1 SP - 267 EP - 73 JF - Physiology & behavior JO - Physiol Behav VL - 139 N2 - Previous studies have shown that while magnesium, an antagonist of the glutamate subtype of N-methyl-D-aspartate receptors, possesses analgesic properties, it can induce writhing in rodents. The aim of this study was to determine the effect and mechanism of action of local (intraplantar) administration of magnesium sulfate (MS) on the paw withdrawal threshold (PWT) to mechanical stimuli. The PWT was evaluated by the electronic von Frey test in male Wistar rats. Tested drugs were either co-administered intraplantarly (i.pl.) with MS or given into the contralateral paw to exclude systemic effects. MS at doses of 0.5, 1.5, 3 and 6.2 mg/paw (i.pl.) induced a statistically significant (as compared to 0.9% NaCl) and dose-dependent mechanical hyperalgesia. Only isotonic MS (250 mmol/l or 6.2% or 6.2 mg/paw) induced mechanical hyperalgesia that lasted at least six hours. Isotonic MS-induced mechanical hyperalgesia was reduced in a dose-dependent manner by co-injection of camphor, a non-selective TRPA1 antagonist (0.3, 1 and 2.5 μg/paw), MK-801, a NMDA receptor antagonist (0.001, 0.025 and 0.1 μg/paw), L-NAME, a non-selective nitric oxide (NO) synthase inhibitor (20, 50 and 100 μg/paw), ARL 17477, a selective neuronal NOS inhibitor (5.7 and 17 μg/paw), SMT, a selective inducible NOS inhibitor (1 and 2.78 μg/paw), and methylene blue, a guanylate cyclase inhibitor (5, 20 and 125 μg/paw). Drugs injected into the contralateral hind paw did not produce significant effects. These results suggest that an i.pl. injection of MS produces local peripheral mechanical hyperalgesia via activation of peripheral TRPA1 and NMDA receptors and peripheral production of NO. SN - 1873-507X UR - https://www.unboundmedicine.com/medline/citation/25449407/TRPA1_NMDA_receptors_and_nitric_oxide_mediate_mechanical_hyperalgesia_induced_by_local_injection_of_magnesium_sulfate_into_the_rat_hind_paw_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0031-9384(14)00560-5 DB - PRIME DP - Unbound Medicine ER -