B.N. Greenwood

Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines.

Proinflammatory cytokines act at receptors in the CNS to alter physiological and behavioral responses. Exposure to stressors increases both peripheral and central proinflammatory cytokines, yet the mechanism(s) of induction remain unknown. Experiments here examined the role of catecholamines in the in vivo induction of proinflammatory cytokines following tailshock stress. Rats were pretreated i.p. with 2.0 mg/kg prazosin (alpha1-adrenoceptor antagonist), 10.0 mg/kg propranolol (beta-adrenoceptor antagonist), or 5.0 mg/kg labetalol (alpha1- and beta-adrenoceptor antagonist) 30 min prior to tailshock exposure and plasma interleukin-1beta (IL-1beta) and IL-6, along with tissue interleukin-1beta from the hypothalamus, hippocampus, and pituitary were measured immediately following stressor termination. Prazosin attenuated stress-induced plasma IL-1beta and IL-6, but had no effect on tissue IL-1beta levels, while propranolol attenuated plasma IL-6 and blocked tissue IL-1beta elevation, and labetalol, which cannot cross the blood-brain barrier, attenuated plasma IL-1beta and IL-6, blocked pituitary IL-1beta, but had no effect on central tissue IL-1beta levels. Furthermore, administration of 50.0 mg/kg N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride, a neurotoxin that lesions neural projections from the locus coeruleus, prevented stress-induced elevation in hippocampal IL-1beta, a region highly innervated by the locus coeruleus, but had no effect on hypothalamic IL-1beta, a region that receives few locus coeruleus projections. Finally, i.p. injection of 5.0 mg/kg isoproterenol (beta-adrenoceptor agonist) was sufficient to induce circulating IL-1 and IL-6, and tissue IL-1beta. These data suggest catecholamines play an important role in the induction of stress-induced proinflammatory cytokines and that beta-adrenoceptors are critical for tissue IL-1beta induction, while both alpha- and beta-adrenoceptors contribute to the induction of plasma cytokines.

Voluntary freewheel running selectively modulates catecholamine content in peripheral tissue and c-fos expression in the central sympathetic circuit following exposure to uncontrollable stress in rats

Modulation of sympathetic drive to the spleen is one potential mechanism whereby physical activity prevents stress-induced splenic immune suppression in rats. The current study tested the hypothesis that voluntary freewheel running reduces peripheral sympathetic drive by modulating stress-induced activity of brain regions synaptically linked to sympathetically innervated peripheral organs, including the adrenals and spleen. To this end, adrenal and splenic catecholamine content and activity of the central sympathetic circuit indexed by c-Fos protein induction, elicited by acute exposure to inescapable tail shock, were measured. Stressor exposure depleted adrenal and splenic norepinephrine content and elicited a robust increase in c-Fos in the brains of sedentary rats. Physical activity status had no effect on adrenal norepinephrine content. Indicative of attenuated sympathetic drive to the spleen, however, 6 weeks of voluntary freewheel running diminished stress-induced splenic norepinephrine depletion, and significantly attenuated stress-induced c-Fos in specific brain regions responsible for sympathetic regulation, including tyrosine hydroxylase-immunoreactive neurons of the locus coeruleus, A5 cell group and rostral ventrolateral medulla. Results suggest that voluntary activity attenuates sympathetic drive to the spleen during stressor exposure by selectively modulating stress-induced activity of the central sympathetic circuit. The attenuation of sympathetic responses observed in this study may be one important mechanism for the protective effect of physical activity against stress-related illness and immunosuppression.

Repeated fear-induced diurnal rhythm disruptions predict PTSD-like sensitized physiological acute stress responses in F344 rats.

To identify objective factors that can predict future sensitized stress responses, thus allowing for effective intervention prior to developing sensitization and subsequent stress‐related disorders, including post‐traumatic stress disorder (PTSD).

(464) Prior voluntary wheel running is protective for neuropathic-like pain

Transformed migraine (TM) is a chronic, daily headache, with vascular quality. Patients usually use large doses of analgesics and experience withdrawal headaches. Cervicogenic migraine, on the other hand, is a secondary headache due to an underlying structural problem in the head or neck. The objective of this study is to evaluate the effectiveness of cervical facets infiltration of C2-3 in the treatment of transformed migraine (TM) plus cervicogenic component. 30 patients were evaluated at the Pain & Headache Center, IMC, KSA, according to IHS classification. Patients were allocated to receive either cervical infiltration of C2-# facets on the same side of migraine (13); or oral bridge therapy (Eletriptan and Etoricoxib) which was administered daily for 15 days, and which was followed by Topiramate 100mg daily for 6 months as a preventive therapy in both groups. Inclusive criteria: 10 males, 20 females; ages 30-50 years, with amean of 40. Exclusive criteria: pediatrics; patients older than 50, with uncontrolled diabetes, blood pressure, other neurological deficits; or pregnancy. Average symptomatic improvement of 78%, according to numeric pain scale, was recognized in patients receiving cervical facets infiltration therapy and appreciated within 10-20 days of therapy. However, an average improvement of 58% was recognized by patients receiving oral bridge therapy and appreciated within one month of therapy. Patients who received cervical facets infiltration showed more rapid and significant symptomatic improvement of their headache after the treatment as compared to the oral bridge therapy.