title: Agmatine attenuates neuropathic pain in sciatic nerve ligated rats: modulation by hippocampal sigma receptors.
abstract: Present study investigated the influence of the sigma (σ₁ and σ₂) receptors within hippocampus on the agmatine induced antinociception in neuropathic rats. Animals were subjected to sciatic nerve ligation for induction of neuropathic pain and observed the paw withdrawal latency in response to thermal hyperalgesia, cold allodynia and the mechanical hyperalgesia. Intrahippocampal (i.h.) as well as intraperitoneal (i.p.) administration of agmatine attenuated neuropathic pain in sciatic nerve ligated rats. Intrahippocampal administration of σ₁ agonist (+)-pentazocine or σ₂ agonist PB28 sensitized whereas, σ₁ antagonist BD1063 or σ₂ antagonist SM21 potentiated antinociceptive effect of agmatine. The behavioral effects correlated with hippocampal tumor necrosis factor-α (TNF-α) levels observed by western blot analysis. These results suggest that both the σ₁ and σ₂ receptor subunits within hippocampus play an important role in antinociceptive action of agmatine against neuropathic pain.
authors.affiliation: Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra 441002, India.
authors.forename: Nandkishor Ramdas
authors.initials: NR
authors.lastname: Kotagale
authors.forename: Saurabh Haridas
authors.initials: SH
authors.lastname: Shirbhate
authors.forename: Pradeep
authors.initials: P
authors.lastname: Shukla
authors.forename: Rajesh Ramesh
authors.initials: RR
authors.lastname: Ugale
mesh_terms: D000376:Agmatine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008026:Ligation / Q000009:adverse effects; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D059225:Nociception / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012584:Sciatic Nerve / Q000601:surgery*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017480:Receptors, sigma; D014409:Tumor Necrosis Factor-alpha; D000376:Agmatine
keywords: Agmatine; Allodynia; Hippocampus; Hyperalgesia; Neuropathic pain; Sigma Receptor; TNF-α