Experimental endotoxemia as a model to study neuro-immune mechanisms in human visceral and somatic pain

Abstract

Although hyperalgesia is a presumed component of sickness behavior, little experimental data exist thus far assessing effects of systemic immune activation on pain in humans. We previously demonstrated that experimentally induced endotoxemia leads to visceral hyperalgesia in healthy humans (Benson et al., Pain 2012;153(4):794–9). Based on these initial findings, we designed the present study to complement and extend our knowledge about effects of endotoxemia not only on visceral but also on somatic pain responses. In this ongoing study, we have implemented a randomized, placebo-controlled between-group design. Following baseline, healthy males receive an intravenous injection of either lipopolysaccharide (LPS group; 0.4 ng/kg) or saline (control group). Visceral sensory and pain thresholds were assessed using pressure-controlled rectal distensions, and somatic pain was induced by pinprick stimulation. Subjective painfulness of rectal and somatic stimuli were evaluated using visual analogue scales. Blood samples were collected before and 1, 2, 3, 4, and 6 h after injection to characterize changes in immune parameters including proinflammatory cytokines. LPS administration induced the expected acute inflammatory response as evidenced by significant increases in circulating TNF-alpha, IL-6, and body temperature (all p < .001). Preliminary results show that LPS-treated subjects rated visceral stimuli as significantly more painful compared to controls ( p < .05), whereas no differences were observed for visceral thresholds and pinprick stimulation. These findings support the relevance of inflammatory processes in the pathophysiology of human visceral hyperalgesia and underscore the need for studies to further elucidate immune-to-brain communication in chronic pain conditions including the functional gastrointestinal disorders.