Nociceptive behaviour upon modulation of mu-opioid receptors in the ventrobasal complex of the thalamus of rats.
The role of mu-opioid receptors (MORs) in the inflammatory pain processing mechanisms within the ventrobasal complex of the thalamus (VB) is not well understood. This study investigated the effect of modulating MOR activity upon nociception, by stereotaxically injecting specific ligands in the VB. Nociceptive behaviour was evaluated in two established animal models of inflammatory pain, by using the formalin (acute and tonic pain) and the ankle-bend (chronic monoarthritic pain) tests. Control (saline intra-VB injection) formalin-injected rats showed acute and tonic pain-related behaviours. In contrast, intrathalamic administration of [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin acetate (DAMGO), a MOR-specific agonist, induced a statistically significant decrease of all tonic phase pain-related behaviours assessed until 30-35min after formalin hind paw injection. In the acute phase only the number of paw-jerks was affected. In monoarthritic rats, there was a noticeable antinociceptive effect with approximately 40min of duration, as denoted by the reduced ankle-bend scores observed after DAMGO injection. Intra-VB injection of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP), a specific MOR antagonist, or of CTOP followed, 10min after, by DAMGO had no effects in either formalin or ankle-bend tests. Data show that DAMGO-induced MOR activation in the VB has an antinociceptive effect in the formalin test as well as in chronic pain observed in MA rats, suggesting an important and specific role for MORs in the VB processing of inflammatory pain.
Pozza
Daniel Humberto
DH
Instituto de Histologia e Embriologia, Faculdade de Medicina, Universidade do Porto, Portugal IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal Serviço de Bioestatística e Informática Médica, Faculdade de Medicina, Universidade do Porto, Portugal Centro de Investigação em Tecnologias e Sistemas de Informação em Saúde - CINTESIS, Universidade do Porto, Portugal.
Potes
Catarina Soares
CS
Barroso
Patrícia Araújo
PA
Azevedo
Luís
L
Castro-Lopes
José Manuel
JM
Neto
Fani Lourença
FL
D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D000842:Ankle / Q000294:innervation / Q000503:physiopathology; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives; D013997:Time Factors; D020651:Ventral Thalamic Nuclei / Q000187:drug effects / Q000378:metabolism*
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin