Growing evidence suggests that the interactions between astrocytes and neurons exert important functions in the central sensitization of the spinal cord dorsal horn in rodents with diabetes and neuropathic pain (DNP). However, it still remains unclear how signal transmission occurs in the spinal cord dorsal horn between astrocytes and neurons, especially in subjects with DNP. Chemokine CXC receptor 4 (CXCR4) plays critical roles in DNP, and connexin 43 (CX43), which is also primarily expressed by astrocytes, contributes to the development of neuropathy. We thus postulated that astrocytic and neuronal CXCR4 induces and produces inflammatory factors under persistent peripheral noxious stimulation in DNP, while intercellular CX43 can transmit inflammatory stimulation signals. The results showed that streptozotocin‐induced type 1 diabetic rats developed heat hyperalgesia and mechanical allodynia. Diabetes led to persistent neuropathic pain. Diabetic rats developed peripheral sensitization at the early phase (2 weeks) and central sensitization at the late phase (5 weeks) after diabetes induction. Both CXCR4 and CX43, which are localized and coexpressed in neurons and astrocytes, were enhanced significantly in the dorsal horn of spinal cord in rats undergoing DNP during late phase of diabetes, and the CXCR4 antagonist AMD3100 reduced the expression of CX43. The nociceptive behavior was reversed, respectively, by AMD3100 at the early phase and by the antioxidant N‐acetyl‐L‐cysteine (NAC) at the late phase. Furthermore, rats with DNP demonstrated downregulation of glial fibrillary acidic protein (GFAP) as well as upregulation of c‐fos in the spinal cord dorsal horn at the late phase compared to the controls, and upregulation of GFAP and downregulation of c‐fos were observed upon treatment with NAC. Given that GFAP and c‐fos are, respectively, makers of astrocyte and neuronal activation, our findings suggest that CXCR4 as an inflammatory stimulation protein and CX43 as an intercellular signal transmission protein both may induce neurons excitability and astrocytes dysfunction in developing DNP.

Neuropathic pain (NPP) is a debilitating clinical condition that presently has few effective treatments. NPP is caused by uncontrolled central oxidative stress and inflammation. Preliminary studies indicate that dexmedetomidine (DEX), an agonist of the alpha-2 adrenergic receptor, is beneficial for treating NPP. In this paper, the effects of administering DEX around injured nerves in a chronic constriction injury- (CCI-) induced neuropathic pain mouse model are investigated. According to the results, the perineural DEX significantly reversed the decline in the mechanical threshold and thermal latency in CCI mice ( ). In the peripherally affected ischiadic nerve, the perineuronal DEX upregulated the expressions of pAMPK, OPA1, and SNPH but not Drp1 or KIF5B. The aforementioned effects of administering DEX can be partially reversed by compound C, a selective and reversible inhibitor of AMP-activated protein kinase (AMPK). Furthermore, it was found that perineural DEX significantly inhibited the CCI-induced upregulation of the immediate early gene c-Fos, overexpression of the inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), attenuation of the NADH dehydrogenase complexes I, II, III, and IV, and the repression of ATP, SOD, and GSH in the dorsal horn of the spinal cord (DHSC) ( ). These findings indicate that perineuronal DEX protected the injured ischiadic nerves and attenuated neuropathic pain via AMPK activation to improve energy supply in the peripheral injured nerves, alleviate the inflammatory factor release, and inhibit oxidative stress in the DHSC.

Objectives: To investigate the efficacy and safety of an improved ultrasound-guided pulsed radiofrequency (PRF) and nerve block (NB) for patients with pudendal neuralgia (PN). Methods: This retrospective analysis included 88 adults with PN treated in the Pain Department of Southwest Hospital from November 2011 to June 2021, with treatment including NB (n = 40) and PRF (n = 48). The primary outcome variable was pain severity, measured by a standardized visual analog scale (VAS). VAS values were collected at 1, 3, 7, and 14 days and 1 and 3 months after patients were treated with NB or PRF. Results: Compared with patients treated with NB (n = 40) and those treated with PRF (n = 48), no significant difference in pain reduction was observed in the short term (p = 0.739 and 0.981, at 1 and 3 days, respectively); however, in the medium and long term (1 to 3 months), there were statistically significant improvements in the PRF group over the NB group (p < 0.001). Moreover, it was noted that the average pain severity of primary PN and PN due to sacral perineurial cyst was significantly reduced with PRF therapy in the medium and long term when compared to other secondary PNs, including surgery, trauma, and diabetes. Discussion: The ultrasound-guided, improved, and innovative PRF/NB puncture path technique allows for gentler stimulation and faster identification of the pudendal nerve. The PRF technique may provide better treatments for primary PN and sacral perineurial cyst causing secondary PN in the medium and long term.

Introduction: Adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) can influence energy metabolism. Energy metabolism imbalance is closely associated with the occurrence of neuropathic pain (NeP). Rs10789038 and rs2796498 are genetic polymorphisms of PRKAA2, the gene encoding AMPK, which is closely related to energy metabolism imbalance. This study aimed to explore the relationship between PRKAA2 and postherpetic neuralgia (PHN) in the southwestern Chinese Han population. Methods: This study enrolled 132 PHN patients and 118 healthy subjects. The rs10789038 and rs2796498 PRKAA2 genotypes were identified in all participants. The association between these single nucleotide polymorphisms and PHN susceptibility was evaluated in the dominant and recessive models. Haplotype analysis of patients with PHN and healthy controls was performed. Results: The PHN patients were older than the healthy subjects (P < 0.05); however, the other clinical characteristics between two groups were not significantly different (all P > 0.05). Genotypes and allele frequencies differed significantly between PHN patients and healthy subjects in the rs10789038 polymorphism (P < 0.05), but not in rs2796498 (P > 0.05). In addition, the GG haplotype of rs10789038-rs2796498 correlated negatively with PHN occurrence in haplotype analysis (P < 0.05). Conclusion: PHN occurrence may be related to the PRKAA2 rs10789038 A>G genetic polymorphism in the southwestern Chinese Han population.