BackgroundPeripheral nerve injury leads to changes in gene expression in primary sensory neurons of the injured dorsal root ganglia. These changes are believed to be involved in neuropathic pain genesis. Previously, these changes have been identified using gene microarrays or next generation RNA sequencing with poly-A tail selection, but these approaches cannot provide a more thorough analysis of gene expression alterations after nerve injury.MethodsThe present study chose to eliminate mRNA poly-A tail selection and perform strand-specific next generation RNA sequencing to analyze whole transcriptomes in the injured dorsal root ganglia following spinal nerve ligation. Quantitative real-time reverse transcriptase polymerase chain reaction assay was carried out to verify the changes of some differentially expressed RNAs in the injured dorsal root ganglia after spinal nerve ligation.ResultsOur results showed that more than 50 million (M) paired mapped sequences with strand information were yielded in each group (51.87 M–56.12 M in sham vs. 51.08 M–57.99 M in spinal nerve ligation). Six days after spinal nerve ligation, expression levels of 11,163 out of a total of 27,463 identified genes in the injured dorsal root ganglia significantly changed, of which 52.14% were upregulated and 47.86% downregulated. The largest transcriptional changes were observed in protein-coding genes (91.5%) followed by noncoding RNAs. Within 944 differentially expressed noncoding RNAs, the most significant changes were seen in long interspersed noncoding RNAs followed by antisense RNAs, processed transcripts, and pseudogenes. We observed a notable proportion of reads aligning to intronic regions in both groups (44.0% in sham vs. 49.6% in spinal nerve ligation). Using quantitative real-time polymerase chain reaction, we confirmed consistent differential expression of selected genes including Kcna2, Oprm1 as well as lncRNAs Gm21781 and 4732491K20Rik following spinal nerve ligation.ConclusionOur findings suggest that next generation RNA sequencing can be used as a promising approach to analyze the changes of whole transcriptomes in dorsal root ganglia following nerve injury and to possibly identify new targets for prevention and treatment of neuropathic pain.

Background: Studies of radiofrequency ablation (RFA) of genicular nerves have reportedly significantly decreased pain up to 3 months post ablation, but no longer term effects have been reported. We performed an analysis of long-term pain relief of 31 RFA procedures of the genicular nerves to analyze the degree of pain relief past 3 months, culminating at 6 months. Objective: To evaluate the long term efficacy of genicular nerve ablation for management of chronic knee pain due to osteoarthritis. Study Design: Chart review and study design was approved by Newark Health Sciences IRB. Chart review and follow-up was performed on all patients who underwent genicular nerve RFA during the period of February 2014 through August of 2015. During this inclusion period 41 genicular nerve RFAs were performed on 31 patients, 5 patients received RFA procedure in both knees. Patient follow-up was performed via telephone interview or in-office visit at least 3 months and 6 months post RFA. Settings: Procedures were performed in Medical Special Procedures at University Hospital in Newark, NJ, and the Pain Management Center at Overlook Medical Arts Center in Summit, NJ. Methods: Chart review and study design was approved by Newark Health Sciences Institutional Review Board. Chart review was performed from February 2014 and continued through August 2015. Patient follow-up was conducted at 3 and at least 6 months post treatment to gauge degree of pain relief (0 – none, 100% – complete), their current day’s pain score, other treatment modalities tried before RFA, and the medications used. Patients were asked to quantify their satisfaction with procedure length, pre-procedure anxiety, complications, and if they would recommend this procedure to others. Primary and secondary goals were the duration of pain relief after RFA, the quality of pain relief, and the efficacy of our approach for RFA of genicular nerves versus prior published techniques. Results: At 3 month follow-up, the average pain relief was 67% improvement from baseline knee pain, 0% being no relief and 100% being complete relief, and average 0 – 10 pain score was 2.9. At 6 month follow-up, of those who described pain relief at 3 months, 95% still described pain relief. This group’s average percent pain relief was 64% and average day’s 0 – 10 pain score 3.3. Limitations: Our study included a retrospective component in chart review followed by prospective follow-up, only 76% of patients were able to participate in the interview process. Furthermore, some patients suffered from other chronic pain ailments, most commonly chronic back pain, which at times disturbed the patient’s ability to focus on solely knee pain. Conclusions: Based on patient interviews and data collection, RFA of genicular nerves can supply on average greater than 60% pain relief in our patient population for as long as 6 months. Key words: Osteoarthritis, knee osteoarthritis, chronic knee pain, radiofrequency ablation, nerve ablation, genicular nerves, long-term pain relief

BackgroundChronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear.ResultsIn this study, we showed that pre- or post-surgical exposure to immobilization 6 h daily for three consecutive days did not change basal responses to mechanical, thermal, or cold stimuli or peak levels of incision-induced hypersensitivity to these stimuli; however, immobilization did prolong the duration of incision-induced hypersensitivity in both male and female rats. These phenomena were also observed in post-surgical exposure to forced swimming 25 min daily for 3 consecutive days. Short-term stress induced by immobilization was demonstrated by an elevation in the level of serum corticosterone, an increase in swim immobility, and a decrease in sucrose consumption. Blocking this short-term stress via intrathecal administration of a selective glucocorticoid receptor antagonist, RU38486, or bilateral adrenalectomy significantly attenuated the prolongation of incision-induced hypersensitivity to mechanical, thermal, and cold stimuli.ConclusionOur results indicate that short-term stress during the pre- or post-operative period delays postoperative pain recovery although it does not affect basal pain perception. Prevention of short-term stress may facilitate patients’ recovery from postoperative pain.

Patients often fail to attend appointments in chronic pain clinics for unknown reasons. We hypothesized that certain patient characteristics predict failure to attend scheduled appointments pointing to systematic barriers to access chronic pain services for certain underserved populations. We collected retrospective data from a longitudinal observational cohort of patients at an academic pain clinic in Newark, New Jersey. To examine the effect of demographic factors on appointment status, we fit a marginal logistic regression using generalized estimating equations with exchangeable correlation. 1394 patients with 3488 total encounters between January 1, 2006 and December 31, 2009 were included. Spanish spoken as a primary language (alternatively Hispanic or other race) and living between five and ten miles from the clinic were associated with reduced odds of arriving for an appointment; making an appointment for a particular complaint such as cancer pain or back pain, an interventional pain procedure scheduled in connection with the appointment, unemployed status, and continuity of care (as measured by office visit number) were associated with increased odds of arriving. Spanish spoken as primary language and distance to the pain clinic predicted failure to attend a scheduled appointment in our cohort. If these constitute systematic barriers to access, they may be amendable to targeted interventions. Perspective We identified certain patient characteristics, specifically Spanish spoken as primary language and geographic distance from the clinic, that predict failure to attend an inner-city chronic pain clinic. These identified barriers to access chronic pain services may be modifiable by simple cost effective interventions.

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