Inflammatory pain in peripheral tissue depends on the activation of the TNF-α type 1 receptor in the primary afferent neuron.

The mechanism underlying the role of tumor necrosis factor alpha (TNF-α) in the development of inflammatory hyperalgesia has been extensively studied, mainly the role of TNF-α in the release of pro-inflammatory cytokines. The current concept relies in the fact that TNF-α stimulates the cascade release of other pro-inflammatory cytokines, such as IL-1ß, IL-6, and IL-8 (CINC-1 in rats), triggering the release of the final inflammatory mediator prostaglandin E2 (PGE2 ) and sympathetic amines that directly sensitize the nociceptors. However, this may not be the sole mechanism involved as the blockade of TNF-α synthesis by thalidomide prevents hyperalgesia without interrupting the synthesis of IL-1ß, IL-6, and CINC-1. Therefore, we hypothesized that activation of TNF-α receptor type 1 (TNFR1) by TNF-α increases nociceptors' susceptibility to the action of PGE2 and dopamine. We have found out that intrathecal administration of oligodeoxynucleotide-antisense (ODN-AS) against TNFR1 or thalidomide prevented carrageenan-induced hyperalgesia. The co-administration of TNF-α with a subthreshold dose of PGE2 or dopamine that does not induce hyperalgesia by itself in the hind paw of Wistar rats pretreated with dexamethasone (to prevent the endogenous release of cytokines) induced a robust hyperalgesia that was prevented by intrathecal treatment with ODN-AS against TNFR1. We consider that the activation of neuronal TNFR1 by TNF-α decisively increases the susceptibility of the peripheral afferent neuron to the action of final inflammatory mediators - PGE2 and dopamine - that ultimately induce hyperalgesia. This mechanism may also underlie the analgesic action of thalidomide.

Raman spectroscopy of dorsal root ganglia from streptozotocin-induced diabetic neuropathic rats submitted to photobiomodulation therapy.

In this study, we used Raman spectroscopy as a new tool to investigate pathological conditions at the level of chemical bond alterations in biological tissues. Currently, there have been no reports on the spectroscopic alterations caused by diabetic neuropathy in the dorsal root ganglia (DRG). DRG are a target for the treatment of neuropathic pain, and the need for more effective therapies is increasing. Photobiomodulation therapy (PBMT) through infrared low-level laser irradiation (904 nm) has shown analgesic effects on the treatment of neuropathy. Thus, the aim of this study was to use Raman spectroscopy to characterize the spectral DRG identities of streptozotocin (STZ)-induced diabetic neuropathic (hyperalgesic) rats and to study the influence of PBMT over such spectra. Characteristic DRG peaks were identified at 2704, 2850, 2885, 2940, 3061 and 3160 cm-1 , whose assignments are CH2 /CH3 symmetric/asymmetric stretches, and C─H vibrations of lipids and proteins. DRG from hyperalgesic rats showed an increased normalized intensity of 2704, 2850, 2885 and 3160 cm-1 . These same peaks had their normalized intensity reduced after PBMT treatment, accompanied by an anti-hyperalgesic effect. Raman spectroscopy was able to diagnose spectral alterations in DRG of hyperalgesic rats and the PBMT reduced the intensity of hyperalgesia and the altered Raman spectra.