Pulsed radiofrequency (PRF) has been reported to be effective in the treatment of several types of pain. The mechanism of action, however, is not well known. In a recent study, the antinociceptive effects of acute thermal pain were shown to be mediated via descending pain inhibitory pathways. In this study we observed an analgesic effect of PRF treatment in an adjuvant induced inflammatory pain model in rats. In this model, sciatic nerves were treated with PRF at 37 degrees and 42 degrees , which inhibited hyperalgesia in the inflammatory groups when compared to RF and sham treatment. This effect was attenuated after intrathecal administration of the alpha2-adrenoceptor antagonist yohimbine, the selective 5-HT3 serotonin receptor antagonist MDL72222, and the non-selective serotonin receptor antagonist methysergide. All three drugs were found to significantly inhibit the analgesic effect of PRF. The results suggest that the analgesic action of PRF involves the enhancement of noradrenergic and serotonergic descending pain inhibitory pathways.

This study demonstrates that LLLT produces analgesic effects in a rat model of peripheral inflammation. We further revealed an additional mechanism of LLLT-mediated analgesia via enhancement of peripheral endogenous opioids. These findings suggest that LLLT induces analgesia in rats by enhancing peripheral endogenous opioid production in addition to previously reported mechanisms.

Previous studies suggest that the blockade of beta-adrenoceptors augments the release of inflammatory regulators in response to proinflammatory stimuli. High-mobility group box 1 (HMGB-1) is a key mediator in the development of sepsis. We investigated whether landiolol, a short-acting selective beta1-adrenoceptor-blocking agent, can attenuate acute lung injury and cardiac dysfunction in a rat model of endotoxin-induced sepsis. We administered LPS i.v. to rats, with or without simultaneous treatment with landiolol (0.1 mg/kg per min). After the induction of sepsis by LPS treatment, we measured cytokine and HMGB-1 levels in the serum and lung tissue. In addition, we performed histopathology, determined wet-to-dry weight ratios, and measured cardiac function and cell signaling in the lung. Cotreatment with landiolol was associated with significantly less severe disease, as assessed by lung histopathology and cardiac function metrics. Serum and lung HMGB-1 levels were lower over time among landiolol-treated animals. Furthermore, nuclear factor-kappaB activity was inhibited by the administration of landiolol. Cotreatment with the selective beta1-adrenoceptor-blocking agent landiolol protects against acute lung injury and cardiac dysfunction in a rat model of LPS-induced systemic inflammation. Treatment was associated with a significant reduction in serum levels of the inflammation mediator HMGB-1 and histological lung damage.

The ACE inhibitor enalapril blocked the LPS-induced inflammatory response and protected against the acute lung injury normally associated with endotoxemia in this rat sepsis model. Given these results, enalapril is a strong candidate as a therapeutic agent for sepsis.

Hyperglycemia is associated with higher HMGB1 levels and lung damage in sepsis. Insulin therapy significantly reduced lung damage, suggesting that management of hyperglycemia with insulin might decrease HMGB1 levels in the serum and lung tissue. One of the mechanisms that could contribute to the inhibition of HMGB1 secretion might be related to the inhibition of NF-kappaB.