Chronic pain is known to induce an amplified aversive reaction to peripheral nociceptive inputs. This enhanced affective response constitutes a key pathologic feature of chronic pain syndromes such as fibromyalgia. However, the neural mechanisms that underlie this important aspect of pain processing remain poorly understood, hindering the development of treatments. Here, we show that a single dose of ketamine can produce a persistent reduction in the aversive response to noxious stimuli in rodent chronic pain models, long after the termination of its anti-nociceptive effects. Furthermore, we demonstrated that this anti-aversive property is mediated by prolonged suppression of the hyperactivity of neurons in the anterior cingulate cortex (ACC), a brain region well known to regulate pain affect. Therefore, our results indicate that it is feasible to dissociate the affective from the sensory component of pain, and demonstrate the potential for low-dose ketamine to be an important therapy for chronic pain syndromes.

Background. Knee osteoarthritis (KOA) is a common degenerative disease associated with joint dysfunction and pain. Ultrasound-guided radiofrequency (RF) may be a promising therapy in the treatment of chronic pain for KOA patients. Objective. To evaluate the efficacy and safety of ultrasound-guided RF treatment for chronic pain in patients with KOA. Design. A systematic review was conducted, and a meta-analysis was carried out when possible. Setting. We examined the studies evaluating the clinical efficiency of ultrasound-guided RF on chronic pain in KOA population. Method. A systematic review for the efficacy and safety of ultrasound-guided RF treatment for pain management of KOA patients was carried out in PubMed, EMBASE, Cochrane Library, Web of Science, Wanfang Data, and China National Knowledge Infrastructure (CNKI) from the date of inception to February 2020, and a meta-analysis was conducted. The primary outcomes of pain intensity (visual analogue scale or numerical rating scale) and knee function [the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)] were evaluated from baseline to various follow-up times by random-effects model. Heterogeneity was assessed by I² statistic and the potential sources of heterogeneity by subgroup and metaregression analyses, respectively. Results. Eight publications with 256 patients were included in the meta-analysis. RF could relieve pain with −4.196 of pooled mean difference and improve knee function by decreasing 23.155 points in WOMAC. Three patients had ecchymosis, two with hypoesthesia and one with numbness after the procedure, and improved within 6 months. Furthermore, study design and treatment target were the sources of heterogeneity by subgroup and metaregression analyses, accounting for 37% and 74% of variances, respectively. Target of genicular nerve achieved better pain relief than intra-articular or sciatic nerve. Sensitivity analysis showed that removal of any single study was unlikely to overturn the findings. Limitations. There were some limitations in the study. Firstly, the small number of relevant studies limited the confidence level of the meta-analysis. Also, the significant heterogeneity may not be explained due to the limited data. Secondly, the direct comparison of two different guidance methods (ultrasound vs. fluoroscopy) for RF therapy is lacking. In addition, the outcomes were blindly assessed in the meta-analysis from all studies according to evaluation of bias, which could affect the reality of the data. Finally, most of the studies only provided short follow-up times, so we could not analyze the long-term effectiveness of ultrasound-guided RF in the treatment of patients with KOA. Conclusions. Ultrasonography is an effective, safe, nonradiative, and easily applicable guidance method for RF in pain relief and functional improvement in KOA patients.

Pain is a complex sensory and affective experience. The current definition for pain relies on verbal reports in clinical settings and behavioral assays in animal models. These definitions can be subjective and do not take into consideration signals in the neural system. Local field potentials (LFPs) represent summed electrical currents from multiple neurons in a defined brain area. Although single neuronal spike activity has been shown to modulate the acute pain, it is not yet clear how ensemble activities in the form of LFPs can be used to decode the precise timing and intensity of pain. The anterior cingulate cortex (ACC) is known to play a role in the affective-aversive component of pain in human and animal studies. Few studies, however, have examined how neural activities in the ACC can be used to interpret or predict acute noxious inputs. Here, we recorded in vivo extracellular activity in the ACC from freely behaving rats after stimulus with non-noxious, low-intensity noxious, and high-intensity noxious stimuli, both in the absence and chronic pain. Using a supervised machine learning classifier with selected LFP features, we predicted the intensity and the onset of acute nociceptive signals with high degree of precision. These results suggest the potential to use LFPs to decode acute pain.

Objective: Peripheral nerve stimulation may be an alternative option to treat severe facial pain. We assessed the application of peripheral nerve stimulation for pain management in patients with herpes zoster ophthalmicus. Method: A retrospective analysis was conducted in patients suffering severe facial pain caused by ophthalmic herpetic lesions. We identified the change in pain severity before and after peripheral nerve stimulation for up to 12 months. Results: Eighteen patients were enrolled. Their mean age was 70.8 ± 9.5 years. Fifteen patients presented with subacute pain for 1–3 months, and three patients suffered postherpetic neuralgia. Dramatic relief from pain was achieved in 83% of patients (15 out of 18) upon initial removal of the stimulator, with pain reduction of > 50%. The long-term analgesic effect was reported at the 6- and 12-month follow-ups, with reductions in the visual analog scale of 4.8 ± 1.2 (n = 18) and 5.4 ± 1.4 (n = 11), respectively. The prevalence of postherpetic neuralgia was 7% (1 out of 15) in the subacute pain group. No obvious adverse effect was observed. Conclusion: Peripheral nerve stimulation may be an efficacious and safe approach for pain control in patients with herpes zoster ophthalmicus.

Introduction Percutaneous balloon compression (PBC) is an effective and safe option for patients with trigeminal neuralgia. A pear-shaped balloon can be used to identify the proper compression of the Gasserian ganglion during the PBC procedure. The aim of this study was to evaluate the relationship between the foramen ovale (FO) size and intraluminal pressure of the pear-shaped balloon. Methods Thirteen patients that presented with classical trigeminal neuralgia were scheduled to undertake PBC surgery at the Pain Department of the Third Xiangya Hospital, Central South University, from November 2020 to April 2021. Three-dimensional computed tomography reconstruction of the skull base was performed to capture the feature of FO preoperatively. The intraluminal pressure was continuously recorded when a pear-shaped balloon was obtained during the procedure. Correlation analysis was calculated to determine the association of the intraluminal balloon pressure with FO parameter. Results All participants reported complete relief of pain at discharge. The enduring analgesic effect of PBC was maintained in all patients with a median follow-up up to 5.5 months (range, 3–8 months). The average intraluminal balloon pressure was 161.5 ± 29.4 kPa at the initial compression (P1), and 134.8 ± 21.5 kPa at the ending of compression (P2), respectively. P1 was significantly correlated with the length (r = 0.61, P = 0.024) of FO. Similarly, a significant and positive correlation was observed between P2 and the length (r = 0.63, P = 0.022) of FO. Conclusions Preoperative assessment of FO may be a potential predictor of intraluminal pressure to reach a pear-shaped balloon during PBC treatment. Narrow FO is associated lower intraluminal balloon pressure.