title: Forebrain medial septum region facilitates nociception in a rat formalin model of inflammatory pain.
abstract: The medial septum is anatomically and functionally linked to the hippocampus, a region implicated in nociception. However, the role of medial septum in nociception remains unclear. To investigate the role of the region in nociception in rats, muscimol, a GABA agonist, or zolpidem, a positive allosteric modulator of GABA(A) receptors, was microinjected into medial septum to attenuate the activity of neurons in the region. Electrophysiological studies in anesthetized rats indicated that muscimol evoked a stronger and longer-lasting suppression of medial septal-mediated activation of hippocampal theta field activity than zolpidem. Similarly, microinjection of muscimol (1 or 2 μg/0.5 μl) into the medial septum of awake rats suppressed both licking and flinching behaviors in the formalin test of inflammatory pain, whereas only the latter behavior was affected by zolpidem (8 or 12 μg/0.5 μl) administered into the medial septum. Interestingly, both drugs selectively attenuated nociceptive behaviors in the second phase of the formalin test that are partly driven by central plasticity. Indeed, muscimol reduced the second phase behaviors by 30% to 60%, which was comparable to the reduction seen with systemic administration of a moderate dose of the analgesic morphine. The reduction was accompanied by a decrease in formalin-induced expression of spinal c-Fos protein that serves as an index of spinal nociceptive processing. The drug effects on nociceptive behaviors were without overt sedation and were distinct from the effects observed after septal lateral microinjections. Taken together, these findings suggest that the activation of medial septum is pro-nociceptive and facilitates aspects of central neural processing underlying nociception.
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Neurobiology Programme, Life Sciences Institute, National University of Singapore, Singapore Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore.
authors: Andy Thiam-Huat
authors: AT
authors: Lee
authors: Mohammed Zacky
authors: MZ
authors: Ariffin
authors: Mingyi
authors: M
authors: Zhou
authors: Jenn Zhou
authors: JZ
authors: Ye
authors: Shabbir M
authors: SM
authors: Moochhala
authors: Sanjay
authors: S
authors: Khanna
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009443:Neuritis / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D020665:Septum of Brain / Q000187:drug effects / Q000502:physiology*