Therapeutic Efficacy of Ultrasound-Guided High-Voltage Long-Duration Pulsed Radiofrequency for Pudendal Neuralgia.

Pudendal neuralgia (PN) is a complex disease with various clinical characteristics, and there is no treatment showing definite effectiveness. This study is aimed at evaluating the clinical efficacy of ultrasound-guided high-voltage long-duration pulsed radiofrequency (PRF) for PN. Two cadavers (one male, one female) were dissected to provide evidence for localization of the pudendal nerve. Patients diagnosed as PN who failed or were intolerant in regular medication were screened for diagnostic local anesthesia block of the pudendal nerve before recruitment. Twenty PN patients were enrolled in this study. In the PRF procedure, the needle tip was inserted medially into the internal pudendal artery under ultrasound guidance. The position of the PRF needle tip was then adjusted by the response of the pudendal nerve to the electrical stimulation within the pudendal area (42°C, a series of 2 Hz, and 20 ms width pulses that lasted for 900 s). Alleviation of pain was assessed by the visual analogue scale (VAS) and sitting time pretreatment and on 7 d, 14 d, 1 m, 2 m, 3 m, and 6 m posttreatment in outpatient follow-up or by telephone interview. Two patients were lost due to intervention-irrelevant reasons. Patients showed significantly decreased VAS scores on 7 d after RFP, compared with pretreatment status (7.0 ± 0.9 vs. 3.2 ± 1.7, P < 0.001). The efficacy remained steady till the end of 6 months, with a final remission rate of 88.9%. Sitting time also significantly lengthened following PRF (7 d, 14 d, 1 m, 2 m, 3 m, and 6 m vs. pretreatment, all P < 0.05). Only short-term ipsilateral involuntary convulsion of the lower extremity was reported in one patient, who recovered within 12 h. Six patients were treated with nonsteroidal drugs for a short time. All patients stopped taking medication finally. In conclusion, the ultrasound-guided high-voltage long-duration PRF approach not only reduced the pelvic pain caused by PN but also improved the quality of life by extending sitting time without nerve injury.

C-X-C Motif Chemokine 10 Contributes to the Development of Neuropathic Pain by Increasing the Permeability of the Blood-Spinal Cord Barrier.

Neuropathic pain is among the most debilitating forms of chronic pain. Studies have suggested that chronic pain pathogenesis involves neuroimmune interactions and blood-spinal cord barrier (BSCB) disruption. However, the underlying mechanisms are poorly understood. We modeled neuropathic pain in rats by inducing chronic constriction injury (CCI) of the sciatic nerve and analyzed the effects on C-X-C motif chemokine 10 (CXCL10)/CXCR3 activation, BSCB permeability, and immune cell migration from the circulation into the spinal cord. We detected CXCR3 expression in spinal neurons and observed that CCI induced CXCL10/CXCR3 activation, BSCB disruption, and mechanical hyperalgesia. CCI-induced BSCB disruption enabled circulating T cells to migrate into the spinal parenchyma. Intrathecal administration of an anti-CXCL10 antibody not only attenuated CCI-induced hyperalgesia, but also reduced BSCB permeability, suggesting that CXCL10 acts as a key regulator of BSCB integrity. Moreover, T cell migration may play a critical role in the neuroimmune interactions involved in the pathogenesis of CCI-induced neuropathic pain. Our results highlight CXCL10 as a new potential drug target for the treatment of nerve injury-induced neuropathic pain.

Analgesic Effect of Methane Rich Saline in a Rat Model of Chronic Inflammatory Pain.

How oxidative stress contributes to neuro-inflammation and chronic pain is documented, and methane is reported to protect against ischemia-reperfusion injury in the nervous system via anti-inflammatory and antioxidant properties. We studied whether methane in the form of methane rich saline (MS) has analgesic effects in a monoarthritis (MA) rat model of chronic inflammatory pain. Single and repeated injections of MS (i.p.) reduced MA-induced mechanical allodynia and multiple methane treatments blocked activation of glial cells, decreased IL-1ß and TNF-α production and MMP-2 activity, and upregulated IL-10 expression in the spinal cord on day 10 post-MA. Furthermore, MS reduced infiltrating T cells and expression of IFN-γ and suppressed MA-induced oxidative stress (MDA and 8-OHDG), and increased superoxide dismutase and catalase activity. Thus, MS may offer anti-inflammatory and antioxidant effects to reduce chronic inflammatory pain.

Bidirectional modulation between infiltrating CD3+ T-lymphocytes and astrocytes in the spinal cord drives the development of allodynia in monoarthritic rats.

Increasing evidence suggests that T cells and glia participate in the process of neuropathic pain. However, little is known about the involvement of T cells or the interaction between glia and T cells at the molecular level. Here we investigated the phenotype of T cell infiltration into the spinal cord in inflammatory pain and explored potential crosstalk between glia and T cells. The establishment of monoarthritis produced T cell infiltration and astrocyte activation, exhibiting similar kinetics in the spinal cord. T-cell-deficient (Rag1-/-) mice significantly attenuated MA-induced mechanical allodynia and GFAP upregulation. Double immunofluorescence staining showed that CD3 mainly colocalized with interferon-gamma (IFN-γ). Western blot and flow cytometry showed that multiple intrathecal administrations of astrocytic inhibitor fluorocitrate decreased IFN-γ-production without decreasing T cell number in the spinal cord. Spinal IFN-γ blockade reduced MA-induced mechanical allodynia and astroglial activation. In contrast, treatment with rIFN-γ directly elicited persistent mechanical allodynia and upregulation of GFAP and pJNK1/2 in naïve rats. Furthermore, rIFN-γ upregulated the phosphorylation of NF-κB p65 in cultured astrocytes vitro and spinal dorsal horn vivo. The results suggest that Th1 cells and astrocytes maintain inflammatory pain and imply that there may be a positive feedback loop between these cells via IFN-γ.