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The bilateral joint-brain connection:pain mechanisms and neuronal control of inflammation

100%

Schaible H. G.

Acta Neurobiologiae Experimentalis

2013

tom 73

nr Suppl.1

Major neuronal mechanisms of inflammatory joint pain are the peripheral and spinal sensitization. We addressed the role of proinflammatory cytokines in neuronal sensitization. A single injection of either TNF-α, interleukin-6, interleukin-1 β and interleukin-17 into the knee joint induced a slowly developing and long-lasting mechanical sensitization of the neurons mimicking longlasting inflammation-evoked sensitization. Vice versa the neutralization of these cytokines reduced hyperalgesia in antigen-induced arthritis. Neutralization of TNF-α significantly reduced mechanical and thermal hyperalgesia, neutralization of IL-1β reduced thermal hyperalgesia, neutralization of IL-17 reduced in particular mechanical hyperalgesia. Neutralization of IL-6 reduced mechanical hyperalgesia upon pretreatment. Spinal cytokines can contribute to inflammation-evoked spinal hyperxcitability. In particular IL-6 was rapidly increased in the spinal cord upon joint inflammation, and neutralization of IL-6 attenuated the development of spinal hyperexcitability. However, the nervous system also influences the inflammatory process. In antigen-induced arthritis in mice chemical sympathectomy or β-adrenergic blockers significantly reduced the magnitude of the acute phase of inflammation. Furthermore, neutralization of spinal TNF-α decreased the inflammatory process in the knee joint. These data suggest that the expression of inflammation is partly dependent on neuronal reflexes.

Interaction of TNFalpha and Interleukin-6 in spinal hyperexcitability of nociceptive neurons

51%

Ebersberger A., Konig C., Moller C., Schaible H. G.

Acta Neurobiologiae Experimentalis

2013

tom 73

nr Suppl.1

Treatment with biologicals neutralizing TNFα was shown to reduce inflammatory hyperalgesia in experimental (Böttger et al. 2008) and human arthritis (Hess et al. 2011). While in the periphery TNFa induced long-lasting sensitization of joint afferents (Richter et al. 2010) the role of spinal TNFα in inflammation-evoked spinal hyperexcitability is possibly indirect because we detected IL-6 after TNFα application in the spinal supernatant. We tested whether spinal effects of TNFα depend on IL-6. We recorded from nociceptive spinal neurons with input from the knee joint in anesthetized rats. We used either normal rats or animals with acute Kaolin/Carrageenan inflammation in the knee as a model of arthritis. The leg was mechanically stimulated at the knee, ankle and paw with innocuous and noxious intensity. During development of inflammation spinal application of an antibody to TNFR1 but not to TNFR2 prevented spinal hyperexcitability. Hyperexcitability during acute inflammation was not reduced by etanercept. When TNFα was applied to the surface of the spinal cord responses to stimulation of the leg increased. Spinal co-application of TNFα and spg130 lead to significant smaller responses to stimulation than application of TNFα alone. In summary TNFα induces spinal hyperexcitability via activation of TNFR1 receptors and subsequent release of spinal IL-6 which is overtaking the maintenance of spinal hyperexcitability

Ograniczanie wyników

2 Acta Neurobiologiae Experimentalis

2 Schaible H. G.

1 Ebersberger A.

1 Konig C.

1 Moller C.

2 2013

Wyniki wyszukiwania

The bilateral joint-brain connection:pain mechanisms and neuronal control of inflammation

Interaction of TNFalpha and Interleukin-6 in spinal hyperexcitability of nociceptive neurons