Retrospectieve praktijkanalyse van tapentadol met vertraagde afgifte bij patiënten met chronische pijn refractair aan sterke opioïden

Retrospective practice analysis of tapentadol prolonged release in patients with chronic pain refractory to strong opioids Tapentadol is a strong opioid with mixed antinociceptive analgesia and inhibition of the descending pain pathway, tested for the management of different types of chronic refractory pain. In daily practice, tapentadol prolonged release (tapentadol PR) is reserved for patients who already received strong opioids with unsatisfactory pain control or severe side effects, or patients who experienced opioid-induced hyperalgesia. The data of patients treated with tapentadol PR in 3 pain centers in Flanders (Belgium) were analyzed. The primary endpoint was the number of patients who continued the tapentadol PR treatment 6 weeks after it started. The secondary endpoints were pain reduction, global perceived effect (GPE) and side effects. Six weeks after the start of the treatment, 83% of the patients continued the therapy. The median reduction in pain score was 2 points on a numeric scale from 0-10. The GPE showed an improvement of 25% to 30% in 52% of the patients. The mean duration of the tapentadol PR treatment was 6.5 months. Only 24% of the patients stopped the treatment because of side effects and 34% due to an unsatisfactory result. Tapentadol PR is a possible addition in the therapeutic arsenal for the treatment of patients with severe chronic pain.

What is the effectiveness of radiofrequency ablation in the management of patients with spinal metastases? A systematic review and meta-analysis

Purpose Spinal metastases are indicative of progressive cancer which can lead to vertebral body fractures and spinal cord compression. Radiofrequency ablation (RFA) treatment is infrequently used in patients with refractory pain. The aim of this systematic review is to determine the clinical efficacy of RFA, with the scope of using it as front-line management of spinal metastases. Methods Electronic databases were searched (to July 2020) for studies evaluating RFA treatment for spinal metastases in adults. Measured outcomes were pain (primary), disability, health-related quality of life (HRQOL), complications, tumour control and mortality. Study inclusion, data extraction and risk of bias using the ROBIN-I tool were assessed. Meta-analysis was conducted for pooled results with homogeneity, and narrative synthesis was conducted otherwise. Results 15 studies were included. RFA reduces pain scores at 3–5 weeks [standardised mean difference (SMD 2.24, 95% confidence intervals (CI) 1.55–2.93], 3–4 months (SMD 3.00, 95% CI 1.11–4.90) and 5–6 months (SMD 3.54, 95% CI 1.96–5.11). RFA is effective in reducing disability/improving HRQOL in the short-term but longer-term efficacy remains unclear. 13.2% cases reported local tumour control failure (2.5 months–5 year follow-up) whereas mortality was 23.6% (follow-up of up to 1 year). Conclusion Low quality evidence has proven RFA to be safe and effective in reducing pain and disability, especially in the short-term. RFA may be routinely implemented in all cases involving refractory pain or radiotherapy-resistant tumours but controlled trials are required to compare the efficacy of RFA to current frontline treatments. PROSPERO protocol registration number: CRD42020202377.

The Clinical Application of Pulsed Radiofrequency Induces Inflammatory Pain via MAPKs Activation: A Novel Hint for Pulsed Radiofrequency Treatment

Pulsed radiofrequency (PRF) works by delivering short bursts of radiofrequency to a target nerve, thereby affecting nerve signal transduction to reduce pain. Although preliminary clinical investigations have shown that PRF treatment can be used safely as an alternative interventional treatment in patients with refractory pain conditions, unexpected damage to a normal nerve/ganglion is still one of the possible complications of using the PRF strategy. Noxious pain may also be triggered if PRF treatment accidentally damages an intact nerve. However, few studies in the literature have described the intracellular modifications that occur in neuronal cells after PRF stimulation. Therefore, in this study, we evaluated the effects of PRF on unimpaired nerve function and investigated the potential mechanisms of PRF-induced pain. Wistar rats were stimulated with 30–60 V of PRF for 6 min, and mechanical allodynia, cold hypersensitivity, cytokine and matrix metalloproteinase (MMP) production, and mitogen-activated protein kinase activity (p38 MAPK, ERK1/2, JNK/SAPK) were analyzed. The results indicated that PRF stimulation induced a significant algesic effect and nociceptive response. In addition, the protein array and Western blotting analyses showed that the clinical application of 60 V of PRF can induce the activation of MAPKs and the production of inflammatory cytokines and MMPs in the lumbar dorsal horn, which is necessary for nerve inflammation, and it can be suppressed by MAPK antagonist treatment. These results indicate that PRF stimulation may induce inflammation of the intact nerve, which in turn causes inflammatory pain. This conclusion can also serve as a reminder for PRF treatment of refractory pain.

Methadone and neuropathic cancer pain subcomponents: a prospective cohort pilot study

Forty per cent of cancer pain associate neuropathic and nociceptive pain simultaneously, and refractory pain affects 15% of cancer pain. Methadone is an effective opioid in treating nociceptive pain and could have an effect on neuropathic pain. Uncertainty remains on its effects on the different subcomponents of neuropathic pain.ObjectivesTo identify which subcomponents of neuropathic cancer pain are addressed using methadone.MethodsAn observational prospective cohort study of palliative care inpatients after rotation for refractory neuropathic cancer pain. Pain intensity was assessed weekly for 28 days, using a Visual Analogue Scale (VAS) and the Neuropathic Pain Symptom Inventory (NPSI).ResultsForty-eight patients were included and 17 completed the 28 days follow-up. VAS pain rating decreased by at least 20 mm in 47% of patients and the pain intensity was significantly lower at day 28 with 53% of patients with a VAS inferior to 4 (p<0.001). The pressure/squeezing component (NPSI score) decreased by more than 2 points in 50% of patients.A linear regression showed allodynia and pressure/squeezing were responsible for the largest part of the overall alleviation of pain (p=0.01).ConclusionsMethadone could significantly improve neuropathic pain through a targeted effect of allodynia and its pressure/squeezing component.

Semidirect targeting–based stereotactic mesencephalotomy for the treatment of refractory pain: a case series

OBJECTIVE One of the few resources for treating medically intractable pain is ablative surgery, but its indications have fallen dramatically over the last decades. One such procedure is mesencephalotomy. This study aims to determine current risks and benefits of MR-guided semidirect targeting–based stereotactic mesencephalotomy. METHODS This was a retrospective study based on a review of the medical records of 22 patients with nociceptive (n = 5), neuropathic (n = 10), or mixed (n = 7) refractory pain treated with unilateral mesencephalotomy alone (17 patients) or associated with bilateral anterior cingulotomy (5 patients) between 2014 and 2021 in the authors’ institutions. The confidence interval adopted in this study was 95%. RESULTS The sample included 12 women and 10 men with ages ranging from 23 to 80 years (mean 55.1 ± 17.1 years). Using MR-guided semidirect targeting, the following structures were targeted: spinoreticulothalamic (neuropathic/mixed pain, n = 17), trigeminothalamic (nociceptive/mixed pain in the face, n = 5), and neospinothalamic (nociceptive/mixed pain in the body, n = 7) pathways. The most common response to macrostimulation was central heat/moderate discomfort. Radiofrequency thermocoagulation was made with 70°C–75°C/60 sec. A total of 86.3% (3 months) and 76.9% (12 months) of the patients achieved excellent or good results (improvement of pain > 50%), presenting with a significant mean pain relief of 80.1% at 3 months and 71.4% at 12 months postoperatively. The addition of bilateral anterior cingulotomy did not improve the results. Patients with upper limb, cervicobrachial, and face pain did significantly better than those with trunk pain. The worst results were seen in patients with neuropathic and/or trunk pain. The surgical failure (pain relief ≤ 25%) and recurrence rates were 9.1% each, apparently related to the use of lower lesioning parameters (70°C/60 sec) and to the presence of neuropathic and/or trunk pain. The morbidity rate was 8%, with both complications (vertical diplopia and confusion/agitation) happening in patients lesioned with 75°C/60 sec. There were no deaths in this series. CONCLUSIONS These results show that contemporary stereotactic mesencephalotomy is an effective, relatively low-risk, and probably underused procedure for treating medically intractable pain. Careful semidirect determination of the target coordinates associated with close attention to electrical macrostimulation responses certainly plays an important role in avoiding complications in most of the procedures. A higher lesioning temperature (75°C) apparently prevents recurrence, but at the cost of an increased risk of complications.

24-month Real-World Study of Spinal Cord Stimulation in Failed Back Surgery Patients with Refractory Pain

BACKGROUND: Failed Back Surgery Syndrome (FBSS) causes disability and lowers health-related quality of life (HRQoL) for patients. Many patients become refractory to Conventional Medical Management (CMM) and Spinal Cord Stimulation (SCS) is advised. However, comparative effectiveness research of both clinical approaches still lacks further evidence. OBJECTIVES: This study describes Comparative Effectiveness Research of CMM versus SCS to provide real world evidence regarding the appropriate means for FBSS management, in terms of Patient-Reported Outcomes Measures. STUDY DESIGN: Naturalistic, pragmatic, prospective observational multicenter SEFUDOCE-study SETTING: FBSS patients attending clinical programmed visits in Pain Unit at Hospital Universitario de La Princesa and at Hospital General Universitario de Alicante (Spain). METHODS: Study evaluates the impact on pain, functional limitation, and HRQoL of CMM versus SCS in the management of FBSS. Patients completed Pain Detect Questionnaire, Oswestry Disability Index, EQ-5D-3L, Medical Outcomes Study Sleep Scale, and Hospital Anxiety and Depression Scale at baseline and at 3, 6, 12, 18 and 24 months. Longitudinal data were analysed with repeated-measures one-way analysis of variance adjusting by confounders. RESULTS: Eighty-five adults patients with FBSS receiving treatment according to current clinical practice were assessed. After 24 months, the PainDETECT Questionnnaire showed that CMM patients maintained similar scores, while SCS patients reduced their overall score (current pain: 6 CMM versus 4.21 SCS, P = 0.0091; intensity strongest pain: 7.77 CMM versus 6.07 SCS, P = 0.0103; average pain: 6.46 CMM versus 4.75 SCS, P = 0.0012). For the Oswestry Disability Index, the Medical Outcomes Study Sleep Scale, and the Hospital Anxiety and Depression Scale no significant inter-group differences were found. EQ-5D utility improved in SCS patients from baseline (baseline: 0.32 CMM versus 0.22 SCS; 24-month: 0.37 CMM versus 0.63 SCS, P = 0.026). Twenty-four month follow-up showed unlikely presence of neuropathic pain and moderate disability in SCS patients, whereas the CMM patients maintained baseline health state. LIMITATIONS: Given the nature of the intervention, conducting a blinded study was not considered practically feasible. A larger sample could also overcome having younger patients in the SCS arm. CONCLUSIONS: SCS may improve the HRQoL and functionality of FBSS patients with refractory pain in the long-term compared to CMM alone. KEY WORDS: Chronic pain management, conventional medical management, failed back surgery syndrome, observational study, spinal cord stimulation