Administration of baclofen, a gamma-aminobutyric acid type B agonist in the thalamic ventrobasal complex, attenuates allodynia in monoarthritic rats subjected to the ankle-bend test.
gamma-Aminobutyric acid type B (GABAB) receptors are involved in the modulation of neuronal activity in response to chronic noxious input. However, the effect of their activation in chronic inflammatory pain in relay thalamic nuclei such as the ventrobasal complex (VB) is not known. In this study, experimental groups of 2, 4, and 14 days monoarthritic (MA) rats were injected with saline (controls) or baclofen (0.875 microg), a specific GABAB receptor agonist, in the VB contralateral to the inflamed joint, and the ankle-bend test was performed. Ankle-bend scores in control animals were near the maximum and were rather constant throughout the entire experimental period, indicating severe nociception. The same was observed in 2 days MA rats injected with baclofen. In the 4 days MA group, the response to baclofen injection was inconsistent among different animals, whereas, in 14 days MA rats, baclofen caused clear antinociceptive effects. Additionally, a 0.5 microg dose of baclofen was tested in 14 days MA rats, but no effect was observed, whereas a 1.25 mug dose produced visible side effects. Baclofen injections that did not target the VB but reached neighboring nuclei were ineffective in reducing nociception. Data demonstrate that the activation of the GABAB receptors by baclofen in the VB of MA rats leads to a decrease of nociception. Moreover, the response depends on the time course of the disease, suggesting the occurrence of different excitatory states of thalamic VB neurons. In conclusion, GABAB receptors in the VB play an important role in chronic inflammatory pain processing.
Potes
Catarina Soares
CS
Institute of Histology and Embryology, Faculty of Medicine and IBMC, University of Porto, Porto, Portugal.
Neto
Fani Lourença
FL
Castro-Lopes
José Manuel
JM
D000818:Animals; D000843:Ankle Joint / Q000187:drug effects* / Q000503:physiopathology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000150:complications; D001418:Baclofen / Q000008:administration & dosage*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality; D058786:GABA-B Receptor Agonists; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D008297:Male; D037061:Metatarsalgia / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000187:drug effects*; D013997:Time Factors
D058786:GABA-B Receptor Agonists; D001418:Baclofen