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Difficult visceral cancer pain is defined as pain that does not improve with conventional non-pharmacological and pharmacological strategies, including opioids and adjuvants, and occurs in up to 15% of patients with cancer. In oncological practice, we must be prepared to establish strategies for dealing with such complex cases. Different analgesic strategies have been described in the literature, including managing refractory pain through palliative sedation; however, this might become a dilemma from a clinical and bioethical point of view in end-of-life situations. We present the case of a young male patient with moderately differentiated intestinal-type adenocarcinoma of the left colon, with intra-abdominal sepsis, and for whom despite the multimodal treatment for difficult visceral cancer pain, the pain was refractory leading to palliative sedation. Difficult visceral cancer pain is a pathology that affects the quality of life of patients and is a challenge for pain specialists, for both pharmacological and non-pharmacological management.

RationaleSpinal cord cysticercosis, an exceptionally rare form of neurocysticercosis (NCC), often leads to refractory neuropathic pain and neurological deficits. Current treatments (e.g., antiparasitics or decompressive surgery) may fail to alleviate symptoms, necessitating alternative strategies. Spinal cord stimulation (SCS) is well-established for chronic pain but has rarely been reported for NCC-related pain.Patient concernsA 69-year-old female presented with an 8-year history of progressively worsening trunk and limb pain (burning sensation, VAS 8/10), sensory abnormalities, and lower limb weakness (MMT 3/5). She had undergone laminectomy for spinal cysticercosis in South Korea, but pain persisted post-operatively.DiagnosesMRI revealed residual cystic lesions with arachnoiditis at T12-L2, consistent with inactive spinal cysticercosis. Electromyography confirmed mixed sensorimotor polyneuropathy.InterventionsAfter multidisciplinary evaluation, a percutaneous SCS electrode was implanted at T10. Intraoperative testing achieved 80% pain coverage. Parameters were titrated post-operatively (frequency: 40 Hz, pulse width: 300 μs).OutcomesAt the 1-week follow-up, the patient reported significant pain relief, with her visual analog scale score dropping to 2 out of 10. Motor strength improved to grade 4 out of 5 on manual muscle testing, and sensory function returned to normal. These benefits persisted at the 3-month follow-up, accompanied by a 75% reduction in opioid requirements, measured in morphine milligram equivalents.LessonsSCS may be a viable option for spinal cysticercosis-induced central neuropathic pain when conventional therapies fail. Its dual benefits (pain relief + functional recovery) warrant further study in NCC-related complications. Early SCS intervention could prevent chronic disability in similar cases.

To investigate the outcome of patients with long-term refractory temporomandibular disorders (TMD) three years after a Norwegian interdisciplinary evaluation program with attention to patient satisfaction, function, pain, and psychosocial variables. The study population consisted of 60 long-term refractory TMD patients who were investigated by a Norwegian interdisciplinary team. A questionnaire that covered medical history, function, pain, lifestyle factors, TMD-status and follow-up from their general medical practitioner (GMP) was sent to the patients three years after the evaluation. Questionnaires that assessed function (Mandibular Functional Index Questionnaire [MFIQ] and Roland Morrison Scale [RMS]), pain intensity (General Pain Intensity questionnaire [GPI]) and psychosocial factors (Hospital Anxiety and Depression scale [HADS]); a 2-item version of the Coping Strategies Questionnaire [CSQ]) were included in the package. Thirty-nine out of 60 TMD patients completed the questionnaires. Improvements in TMD symptoms were reported in 10 patients (26%), were unchanged in 16 patients (41%) and worsened in 13 patients (33%). Only 8 patients (21%) were satisfied with the follow-up of the suggested treatments from their GMP. Significant improvements of symptoms were noted in MFIQ (jaw function), GPI (including pain intensity at maximum and suffering from pain), and CSQ (pain related catastrophizing), in all 39 TMD patients as one group. However, a subgroup analysis showed that the significant improvements were mostly within patients who reported improvement of TMD symptoms. A high pain intensity at baseline was a significant risk factor .79, 95% CI: 1.34, 24.96) for patients who reported worsening of TMD symptoms at follow-up. High pain intensity at baseline was a significant risk factor for poorer recovery three years after an interdisciplinary evaluation. Our data support the notion that improved coping with TMD pain includes both decreased pain intensity, CSQ and MFIQ scores.

Purpose Refractory cancer-induced bone pain (CIBP) affects a patient’s functional capacity and quality of life, but there is limited evidence to guide opioid choice. We assessed the feasibility, tolerability and possible efficacy of methadone rotation (MR) compared to other opioid rotations (OOR) in this cohort. Methods Adults with CIBP and worst pain intensity ≥ 4/10 and/or opioid toxicity graded ≥ 2 on the Common Terminology Criteria for Adverse Events were randomised 1:1 to methadone or another opioid rotation. Standardised assessment tools were used at pre-defined study time points up to 14 days. Results Of 51 eligible participants, 38 (74.5%) consented, and 29 (76.3%, MR: 14, OOR: 15) completed the fourteen days follow-up post-opioid rotation. Both groups displayed significant reduction in average (MR: d  =  − 1.2, p  = 0.003, OOR: d  =  − 0.8, p  = 0.015) and worst pain (MR: d  =  − 0.9, p  = 0.042, OOR: d  =  − 0.6, p  = 0.048) and total pain interference score (MR: d  =  − 1.1, p  = 0.042, OOR: d  =  − 0.7, p  = 0.007). Oral morphine equivalent daily dose was reduced significantly in MR compared to the OOR group ( d  =  − 0.8, p  = 0.05). The incidence of opioid-related adverse events following MR was unchanged but lower in the OOR group ( d  = 0.9, 95% CI 0.1,1.7, p  = 0.022). There were no within-group or between-group differences in satisfaction with analgesia at the end of the study. Conclusion This pilot study demonstrated that MR and OOR in patients with refractory CIBP are feasible, safe and acceptable to patients. Appropriately powered multi-centre randomised controlled studies are needed to confirm the efficacy of MR and OOR in this cohort. Trial registration ACTRN12621000141842 registered 11 February 2021.

Objective. The increasing incidence of cancer survivorship has shifted treatment of cancer-related pain from short-term analgesia to long-term chronic pain management. As a result, alternatives to oral analgesics, such as intrathecal therapy, may be beneficial for patients with cancer-related pain. The authors review the use of intrathecal therapy in the management of cancer-related pain. Methods. The Medline database was searched for English-language articles that included “ziconotide” or “morphine” AND (“cancer” OR “malignant”) AND “intrathecal” in title or abstract. Available abstracts from scientific congresses in the areas of neuromodulation and oncology were also reviewed. Results. Intrathecal therapy provides pain relief with reduced systemic concerns in patients with cancer-related pain. Patients should undergo multidisciplinary evaluation and, in most cases, drug trialing before intrathecal pump implantation. Morphine, an opioid (µ-opioid receptor antagonist), and ziconotide, a nonopioid (selective N-type calcium channel inhibitor), are both approved for intrathecal analgesia; however, tolerance and safety concerns may deter the use of intrathecal morphine. Ziconotide has also shown efficacy for reduction of cancer-related pain; however, proper dosing and titration must be used to prevent adverse events. There is little information available on use of intrathecal therapies specifically in cancer survivors. Conclusions. Treatment of cancer-related pain has shifted toward chronic pain management strategies, especially among cancer survivors. Intrathecal therapy provides an alternate route of administration of chronic pain medications (e.g., morphine and ziconotide) for cancer patients with and without active disease, although additional research is needed to support effectiveness in cancer survivors.

Purpose: To investigate the outcome of patients with long-term refractory temporomandibular disorders (TMD) three years after a Norwegian interdisciplinary evaluation program with attention to patient satisfaction, function, pain, and psychosocial variables. Patients and Methods: The study population consisted of 60 long-term refractory TMD patients who were investigated by a Norwegian interdisciplinary team. A questionnaire that covered medical history, function, pain, lifestyle factors, TMD-status and follow-up from their general medical practitioner (GMP) was sent to the patients three years after the evaluation. Questionnaires that assessed function (Mandibular Functional Index Questionnaire [MFIQ] and Roland Morrison Scale [RMS]), pain intensity (General Pain Intensity questionnaire [GPI]) and psychosocial factors (Hospital Anxiety and Depression scale [HADS]); a 2-item version of the Coping Strategies Questionnaire [CSQ]) were included in the package. Results: Thirty-nine out of 60 TMD patients completed the questionnaires. Improvements in TMD symptoms were reported in 10 patients (26%), were unchanged in 16 patients (41%) and worsened in 13 patients (33%). Only 8 patients (21%) were satisfied with the follow-up of the suggested treatments from their GMP. Significant improvements of symptoms were noted in MFIQ (jaw function), GPI (including pain intensity at maximum and suffering from pain), and CSQ (pain related catastrophizing), in all 39 TMD patients as one group. However, a subgroup analysis showed that the significant improvements were mostly within patients who reported improvement of TMD symptoms. A high pain intensity at baseline was a significant risk factor (OR = 5.79, 95% CI: 1.34, 24.96) for patients who reported worsening of TMD symptoms at follow-up. Conclusion: High pain intensity at baseline was a significant risk factor for poorer recovery three years after an interdisciplinary evaluation. Our data support the notion that improved coping with TMD pain includes both decreased pain intensity, CSQ and MFIQ scores. Keywords: catastrophizing, interdisciplinary, orofacial pain, refractory pain, stress, evaluation

Background Resistance to treatments have been assessed in chronic conditions such as migraine, but not in temporomandibular disorders (TMD). This study aimed to identify factors that influence treatment outcome in patients with myofascial TMD pain. Methods Seventy-two females were divided into three groups: TMD successfully treated (TMD-S, n  = 24), TMD resistant to treatment (TMD-R, n  = 24) and Controls without TMD ( n  = 24). Criteria for resistance included: less than 30% pain reduction after three months of conservative treatment and an average pain intensity > 50 mm (VAS) during the last month. Quantitative sensory testing (QST), psychosocial status and genetic polymorphisms were examined. ANOVA on ranks (psychosocial variables) with Dunn’s test as post-hoc or ANOVA (age and somatosensory variables) with Tukey test as post-hoc test, and Dwass-Steel-Critchlow-Fligner test (genetic variables) were used for univariate groups comparisons. Multivariate statistics were used to identify outcomes that separated the groups. Results QST assessment revealed lower baseline pressure pain threshold and higher wind-up ratio in the trigeminally and spinally innervated areas in the TMD-R group compared with the other groups ( p  = 0.01). Also, the TMD-R group presented higher values in all assessed psychosocial variables ( p  < 0.01) and higher prevalence of the HTR1A polymorphism rs6295 ( p  = 0.02) compared with the other groups at baseline. Multivariate analysis showed that the three variables that distinguished the best between TMD-R and TMD-S were sleeping quality, central sensitization, and depressive symptoms. Conclusion Psychosocial, somatosensory, and genetic alterations are related to unsuccessful treatment response in myofascial TMD patients.

Abstract BACKGROUND Cancer pain, one of the most common symptoms for patients with advanced cancer, is often refractory to maximal medical therapy. A controlled clinical trial is needed to provide definitive evidence to support the use of ablative procedures such as cordotomy for patients with medically refractory cancer pain. OBJECTIVE To assess the efficacy of cordotomy for patients with unilateral advanced cancer pain using a controlled clinical trial study design. The secondary objectives are to define the patient experience of cordotomy for medically refractory cancer pain as well as to determine the utility of magnetic resonance imaging as a non-invasive biomarker for successful cordotomy. METHODS We will undertake a single-institution, double-blind, sham-controlled clinical trial of cordotomy in patients with refractory cancer pain. Patients in the cordotomy arm will undergo a percutaneous computed tomography-guided cordotomy at C1-C2, while patients in the control arm will undergo a similar procedure where the needle will not penetrate the thecal sac. The primary endpoint will be the reduction in pain intensity, as measured by the Edmonton Symptoms Assessment Scale. EXPECTED OUTCOMES We expect that patients randomized to cordotomy will have a significantly greater reduction in pain intensity than those patients randomized to the control surgical intervention. DISCUSSION This randomized clinical trial comparing cordotomy with a control intervention will provide the level of evidence necessary to determine whether cordotomy should be the standard of care intervention for patients with advanced cancer pain.

Background Central neuropathic pain after foramen magnum decompression (FMD) for Chiari malformation type 1 (CM-1) with syringomyelia can be residual and refractory. Here we present a case of refractory central neuropathic pain after FMD in a CM-1 patient with syringomyelia who achieved improvements in pain following spinal cord stimulation (SCS) using fast-acting sub-perception therapy (FAST™). Case presentation A 76-year-old woman presented with a history of several years of bilateral upper extremity and chest-back pain. CM-1 and syringomyelia were diagnosed. The pain proved drug resistant, so FMD was performed for pain relief. After FMD, magnetic resonance imaging showed shrinkage of the syrinx. Pain was relieved, but bilateral finger, upper arm and thoracic back pain flared-up 10 months later. Due to pharmacotherapy resistance, SCS was planned for the purpose of improving pain. A percutaneous trial of SCS showed no improvement of pain with conventional SCS alone or in combination with Contour™, but the combination of FAST™ and Contour™ did improve pain. Three years after FMD, percutaneous leads and an implantable pulse generator were implanted. The program was set to FAST™ and Contour™. After implantation, pain as assessed using the McGill Pain Questionnaire and visual analog scale was relieved even after reducing dosages of analgesic. No adverse events were encountered. Conclusion Percutaneously implanted SCS using FAST™ may be effective for refractory pain after FMD for CM-1 with syringomyelia.

Methadone and ketamine are used in neuropathic pain management. However, the benefits of both drugs association are uncertain in the treatment of neuropathic pain. Our primary objective was test the hypothesis that oral methadone combined with oral ketamine is more effective than oral methadone or ketamine alone in reducing neuropathic pain. We conducted a randomized, double blind, active-controlled parallel-group clinical trial. Forty-two patients with neuropathic pain refractory to conventional therapy were randomly assigned to receive oral methadone (n = 14), ketamine (n = 14), or methadone plus ketamine (n = 14) over a 3-month period. During these 90 days, we observed pain scores using a visual analogical scale (VAS), allodynia, burning/shooting pain, and some side effects. All treatments were effective in reducing pain scores by at least 40%. However, a significant improvement in pain was observed only in the ketamine alone group compared with both the methadone or methadone/ketamine groups. No significant differences were observed among the treatment groups for the reduction of burning or shooting pain, while ketamine alone was more effective than methadone or methadone/ketamine for the reduction of allodynia. Formal assessment for awareness of the allocation was not performed, some co-intervention bias may have occurred, our results could be only relevant to the patient population investigated and the use of VAS as the primary outcome detect changes in pain intensity but not to assess neuropathic pain symptoms. This study indicates that ketamine was better than methadone or methadone/ketamine for treating neuropathic pain.Key words: Multimodal analgesia, refractory pain, NMDA receptor, opioid.