title: Anti-nociceptive effect of IL-12p40 in a rat model of neuropathic pain.
abstract: IL-12p70 is a proinflammatory cytokine secreted by dendritic cells, monocytes and macrophages. It plays a crucial role in cell-mediated immunity by inducing proliferation of T cell and natural killer cells, and enhancing their cytotoxic activity. In adaptive immune response, it acts on naive T cells to differentiate into Th1-type cells. It is composed of two subunits, p35 and p40. The latter can be secreted in the form of monodimer or heterodimer, which is also referred as IL-12p80. Recently IL-12p70 has been proven to locally provoke nociceptive effect in naïve rats. This study investigated pain response following systemic administration of IL-12p70 and IL-12p40 homodimer in chronic neuropathic pain model, induced by chronic constriction injury. The doses tested were IL-12p40 homodimer or IL12p70 at 15, 150 and 1500ng/kg, respectively. Pain was assessed at 1, 4, 7 and 24h after injection, in the form of tactile allodynia and mechanical hyperalgesia. The side effect of sensory motor disability was measured by rotarod performance. By all behavioral measures, IL-12p70 of any dosage, at any time point, had no significant effect on tactile allodynia and mechanical hyperalgesia. A high dose of IL-12p40 homodimer induced significant analgesic effect by the measure of hind paw tactile allodynia from 1h to 4h after injection. Medium and low doses of IL-12p40 homodimer exerted their analgesic effect 4h post injection. Mechanical hyperalgesia, following high and medium doses of IL-12p40 administration, was significantly reduced at 4h after application. Also, no significant sensory motor dysfunction was detected for all dosage for both homodimers. These findings suggest that systemic application of IL-12p40 homodimer induces time-dependent analgesia to mechanical stimulation in rats exposed to neuropathic pain.
authors.affiliation: Department of Diagnostic Sciences, UMDNJ, New Jersey Dental School, Newark, USA.
authors.forename: I-Fang
authors.initials: IF
authors.lastname: Chen
authors.forename: Junad
authors.initials: J
authors.lastname: Khan
authors.forename: Noboru
authors.initials: N
authors.lastname: Noma
authors.forename: Emad
authors.initials: E
authors.lastname: Hadlaq
authors.forename: Sorin
authors.initials: S
authors.lastname: Teich
authors.forename: Rafael
authors.initials: R
authors.lastname: Benoliel
authors.forename: Eli
authors.initials: E
authors.lastname: Eliav
mesh_terms: D000818:Animals; D003250:Constriction; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D053762:Interleukin-12 Subunit p40 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D059225:Nociception / Q000187:drug effects*; D059408:Pain Management; D055503:Protein Multimerization; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
chemical_list: D053762:Interleukin-12 Subunit p40