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Stimulation of the posterior hypothalamic area (PH) produces antinociception in rats and humans, but the precise mechanisms are unknown. The PH forms anatomical connections with the parabrachial area, which contains the pontine A7 catecholamine cell group, a group of spinally projecting noradrenergic neurons known to produce antinociception in the dorsal horn. The aim of the present study was to determine whether PH-induced antinociception is mediated in part through connections with the A7 cell group in female Sprague-Dawley rats, as measured by the tail flick and foot withdrawal latency. Stimulation of the PH with the cholinergic agonist carbachol (125 nmol) produced antinociception that was blocked by pretreatment with atropine sulfate. Intrathecal injection of the α2-adrenoceptor antagonist yohimbine reversed PH-induced antinociception, but the α1-adrenoceptor antagonist WB4101 facilitated antinociception. Intrathecal injection of normal saline had no effect. In a separate experiment, cobalt chloride, which reversibly arrests synaptic activity, was microinjected into the A7 cell group and blocked PH-induced antinociception. These findings provide evidence that the PH modulates nociception in part through connections with the A7 catecholamine cell group through opposing effects. Antinociception occurs from actions at α2-adrenoceptors in the dorsal horn, while concurrent hyperalgesia occurs from actions of norepinephrine at α1-adrenoceptors. This hyperalgesic response likely attenuates antinociception from PH stimulation.

Neuropathic pain contributes to skeletal muscle atrophy and decreases in activity in rats.

Introduction Foot and lower limb pain reported by many adults experiencing homelessness may be due to improper shoes and may contribute to decreased activity and physical functioning. Objective The purpose of this study was to characterize the effects of proper fitting shoes on pain, activity, and foot health in adults experiencing homelessness. Design A pretest–posttest quasi‐experimental pilot study design was used. Sample Twenty‐three out of 30 enrolled participants completed the study and were mostly female, non‐Hispanic, black individuals with high school education or higher. Measurements Eligible participants completed surveys related to pain, foot health, and foot conditions, and a 10‐meter walking test prior to (BASELINE) and after (FINAL) the intervention. Intervention Participants wore properly fitted shoes for 6 weeks and were encouraged to maintain activity levels consistent with activity levels prior to receiving new shoes. Results Pain scores were lower at FINAL versus BASELINE. Participants reported reductions in knee, back and ankle/feet pain. Participants had significant improvements on almost all areas of foot health and had faster gait speed at FINAL versus BASELINE. Minimal changes in foot conditions were observed. Conclusion Proper fitting shoes improve pain, walking speed, and foot health in adults experiencing homelessness with moderate to severe pain.