Treatment Of Complex Regional Pain Syndrome Research Articles

Experience from a single-center study on multimodal medication therapy for patients with complex regional pain syndrome.

Despite the application of various therapeutic methods, pain caused by complex regional pain syndrome (CRPS) is not sufficiently managed and often progresses to a chronic stage. For the systematic and effective treatment of CRPS, we developed an algorithm for multimodal medication therapy based on the established pathophysiology of CRPS to control CRPS-related pain. In this study, we present the outcomes of our novel algorithm for multimodal medication therapy for patients with CRPS, consisting of three major components: multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapy. We retrospectively investigated patients with CRPS who received multimodal therapy. Pain severity scores were evaluated using a numerical rating scale at four time points (P1, pain at initial consultation; P2, pain after oral medication; P3, pain after ketamine treatment; and P4, pain after lidocaine treatment). The effect of the multimodal medication therapy algorithm on pain management was evaluated at each time point. In patients with CRPS, multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapies led to significantly improved pain control (p< 0.05). Additionally, the combination of these three therapies (through the multimodal medication therapy algorithm) resulted in significant pain relief in patients with CRPS (p< 0.05). Our multimodal medication therapy algorithm effectively controlled pain in patients with CRPS. However, further prospective studies with large sample sizes and randomized controlled trials are needed for more accurate generalization.

Remission of hypersensitivity by simple weight load stimuli in a complex regional pain syndrome mouse model.

Painful sensitivity of the hand or foot are the most common and debilitating symptoms of complex regional pain syndrome (CRPS). Physical therapy is standard treatment for CRPS, but evidence supporting its efficacy is minimal and it can be essentially impossible for CRPS patients to actively exercise the painful limb. Using the well-characterized distal tibial fracture CRPS mouse model, we compared the therapeutic effects of several weeks of daily hindlimb loading versus rotarod walking exercise. The effects of loading and exercise were evaluated by weekly testing of hind-paw withdrawal thresholds to von Frey fibers and radiant heat, as well as measurements of paw and ankle edema. At 6 weeks after fracture, the mice were killed and the ipsilateral femur, spinal cord and L4/5 dorsal root ganglia, and hind-paw skin collected for PCR assays and paw skin Immunohistochemistry evaluation. Hindlimb loading reduced hind-paw von Frey allodynia and heat hyperalgesia and edema within a week and these effects persisted for at least a week after discontinuing treatment. These therapeutic effects of loading exceeded the beneficial effects observed with rotarod walking exercise in fracture mice. Levels of nerve growth factor and transient receptor potential vanilloid 1 (TRPV1) immunostaining in the hind-paw skin were increased at 6 weeks after fracture, and both loading and exercise treatment reduced increases. Collectively, these results suggest that loading may be an effective and possibly curative treatment in CRPS patients with sensitivity in the affected limb.

Subtypes of complex regional pain syndrome-a systematic review of the literature.

To systematically identify and summarize possible subtypes of complex regional pain syndrome (CRPS), we searched MEDLINE, Embase, Cochrane, Scopus, and Web of Science for original studies reporting or investigating at least one subtype within a group of patients with CRPS. The search retrieved 4239 potentially relevant references. Twenty-five studies met our inclusion criteria and were included in the analysis. Complex regional pain syndrome phenotypes were investigated based on the following variables: clinical presentation/sensory disturbances, dystonia, skin temperature, disease duration, onset type, CRPS outcome, and neuropsychological test performance. Support was found for the following CRPS subtypes: CRPS type I, CRPS type II, acute CRPS, chronic CRPS, centralized CRPS, cold CRPS, warm CRPS, inflammatory CRPS, dystonic CRPS, nondystonic CRPS, familial CRPS, and nonfamilial CRPS. It is unclear whether these are distinct or overlapping subtypes. The results of this comprehensive review can facilitate the formulation of well-defined CRPS subtypes based on presumed underlying mechanisms. Our findings provide a foundation for establishing and defining clinically meaningful CRPS subtypes, with the ultimate goal of developing targeted and enhanced treatments for CRPS.

The efficacy of oral corticoids in treating complex regional pain syndrome: A retrospective cohort study.

There is growing evidence supporting the role of inflammatory mechanisms in complex regional pain syndrome (CRPS). Corticoids, as most effective anti-inflammatory drugs, are widely used in treating inflammation. The aim of this study was to retrospectively assess the efficacy of oral corticoid treatment in CRPS patients. Patients treated at the center of pain medicine in the Erasmus University Medical Centre between January 2015 and January 2020 were approached to partake in this study. Medical records were screened for age, gender, medical history, duration of CRPS, and CRPS severity score. Also, treatment effect, dose and duration, pain scores (NRS), and side effects were extracted from medical records. In addition, global perceived effect was completed in patients treated with corticoids. Between January 2015 and January 2020, twenty-nine CRPS patients received corticoids and met the inclusion criteria. One extreme outlier was excluded and treatment effect was unknown for one patient. Average daily dose was 28.9 mg (range 10-30 mg) and the mean treatment duration was 10.5 days (7-21 days). Fourteen patients (51.9%) responded positively to treatment and thirteen (48.1%) did not respond. Side effects were reported in five patients (17.9%). Corticoid treatment was effective in more than half of the patients. With only mild side effects reported the treatment also appears to be relatively safe. Further research is needed to investigate the efficacy of corticoids in treating (early) CRPS, preferably in an intervention study.

Virtual reality in managing Complex Regional Pain Syndrome (CRPS): a scoping review.

Complex Regional Pain Syndrome (CRPS) is a severe pain disorder that does not yet have a specific treatment. Patients with CRPS not only suffer from a wide range of symptoms that affect their quality of life but also present psychological affections to the way they see their body and specifically their affected limb. Virtual Reality (VR) modalities have become a targeted treatment for chronic pain and in the case of CRPS, may be a valuable approach to the mechanisms that affect these patients. Using the PRISMA Scoping Review guidelines, we intend to uncover the key information from the studies available about VR modalities in the treatment of CRPS. We focus on the improvement of pain levels, body perception disturbances (BPD), and limb movement/daily function. Our search strategy resulted in 217 articles from PubMed. Twenty were assessed for eligibility and seven were included in the final qualitative synthesis. Of these seven articles, we included a clinical trial, three pilot studies, a blinded randomized controlled trial, a crossover double-blind trial, and a randomized controlled trial. These studies provide important subjective patient findings, along with some statistically significant results in the experiences of VR therapies modulating pain, BPD, and improving limb movement/daily function. However, not all the studies included statistical analysis, and there are contradicting data found from some patients that did not perceive any improvement from VR therapies. We describe the results found in 7 articles that focus on the treatment of CRPS with VR modalities. Overall, the articles have various limitations, but the strategies related to immersive virtual reality, cardiac signaling, body switching and limb modulation have shown the most promising results for pain reduction and BPD improvement. These strategies reflect on pathophysiological mechanisms that are hypothesized to be affected in CRPS patients leading to the chronic pain and BPD that they experience. Not much evidence was found for improvement in limb movement and daily function. This review is a pathway for future studies on this topic and a more extensive data synthesis when more information is available.

Long-term effectiveness and predictors of bisphosphonate treatment in type I complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a painful disease that leads to chronic pain and disability. Bisphosphonates are largely used in the real-life for the treatment of CRPS, but data on long-term effectiveness and its predictors are lacking. We conducted a longitudinal observational study on patients with type I CRPS treated with IV neridronate (100 mg on 4 occasions). Clinical and demographic characteristics were collected at baseline, after 3 months (M3) and after 12 months (M12). Multivariable logistic regression was employed to determine the factors associated with long-term response to treatment. 103 patients with type I CRPS treated with IV neridronate were included in the study. Mean VAS pain at baseline was 79.1 mm and decreased significantly at M3 (-45.9 mm, 95% CI 40.1 to 51.8) and M12 (-61.6 mm, 95% CI 55.3 to 67.9). Hyperalgesia and allodynia resolved in 84.3% and 88.1% of patients at M12. Loss of motion resolved in 53.5% of patients. The predictors of excellent response were gender (male better), predisposing event to CRPS (no event being better than any predisposing event), site of CRPS (lower limb being better), and early response at M3 on VAS pain (2.5 times the chance of being excellent responder every 10 mm decrease). In this real-life study neridronate was associated with rapid and progressive improvement of symptoms of CRPS which was maintained up to 3 years of follow-up. The predictors of excellent response were early response, lower limb localisation, absence of predisposing events and male gender.

Interventional Treatment of Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is a rare but debilitating chronic pain disorder characterized by persistent pain disproportionate to any preceding injury. CRPS can have a significant impact on a person's quality of life, often leading to disability and psychological distress. Despite being recognized for over a century, finding the right treatment for CRPS can be challenging. In this article, we will explore the causes, symptoms, and interventional treatment options for CRPS, as well as the latest research on this complex and often misunderstood condition.

Sub-anaesthetic dose of propofol attenuates mechanical allodynia in chronic post-ischaemic pain via regulation of PTEN/PI3K/IL-6 signalling.

Background: Propofol is an intravenous anaesthetic drug that has been shown to reduce inflammatory pain. Complex regional pain syndrome (CRPS) type I is a pain condition characterized by autonomic, motor and sensory disturbance. The chronic post-ischaemic pain (CPIP) model is a well-established model to recapture CRPS-I syndromes pre-clinically by non-invasive ischaemic-reperfusion (IR) injury. In this study, we investigated the analgesic effects of propofol and underlying mechanisms in mitigating CRPS pain using the CPIP model. Methods: Sub-anaesthetic dose of propofol (25mg/kg) was intravenously delivered to the CPIP model and sham control. Nociceptive behavioural changes were assayed by the von Frey test. Molecular assays were used to investigate expression changes of PTEN, PI3K, AKT and IL-6 underlying propofol-mediated analgesic effects. Pharmacological inhibition was applied for PTEN/PI3K/AKT pathway manipulation. Results: Both pre- and post-operative administration of propofol attenuated mechanical allodynia induced by CPIP. Propofol could modulate PTEN/PI3K/AKT signalling pathway by increasing active PTEN and reducing phosphorylated PI3K, phosphorylated AKT and IL-6 expression in the spinal dorsal horn, which promoted pain relief in the CPIP model. Inhibition of PTEN with bpV abolished the analgesic effects produced by propofol in CPIP mice. Conclusion: Sub-anaesthetic dose of propofol administration resulted in the activation of PTEN, inhibition of both PI3K/AKT signalling and IL-6 production in the spinal cord, which dramatically reduced CPIP-induced pain. Our findings lay the foundation in using propofol for the treatment of CRPS with great therapeutic implications.

Perineural treatment with anti-TNF-α antibody ameliorates persistent allodynia and edema in novel mouse models with complex regional pain syndrome

Complex regional pain syndrome (CRPS) is an intractable chronic pain syndrome with various signs and symptoms including allodynia/hyperalgesia, edema, swelling, and skin abnormalities. However, a definitive therapeutic treatment for CRPS has not been established. In CRPS patients, inflammatory cytokines such as TNF-α and IL-1β have been shown to increase in affected areas, suggesting that these molecules may be potential therapeutic targets for CRPS. Here, we first created a novel CRPS mouse model (CRPS-II-like) via sciatic nerve injury and cast immobilization, which was characterized by mechanical allodynia, local edema, and skin abnormalities, to evaluate the pathophysiology and pharmacotherapy of CRPS. When an anti-TNF-α antibody was consecutively administered near the injured sciatic nerve of CRPS model mice, persistent allodynia and CRPS-related signs in the ipsilateral hindpaw were markedly attenuated to control levels. Perineural administration of anti-TNF-α antibody also suppressed the upregulation of inflammatory cytokines as well as the activation of macrophages and Schwann cells in the injured sciatic nerve. These findings indicate that persistent allodynia and CRPS-related signs in CRPS models are primarily associated with TNF-α-mediated immune responses in injured peripheral nerves, suggesting that perineural treatment with anti-TNF-α antibody might be therapeutically useful.

Effectiveness of Infliximab in Patients with Complex Regional Pain Syndrome: A Case Series.

Complex regional pain syndrome (CRPS) is a multi-mechanism disease, with an exaggerated inflammatory response as an important underlying mechanism. Auto-inflammation can theoretically be combated by anti-inflammatories, such as TNF-α inhibitors. This study's aim was to assess the effectiveness of intravenous infliximab, a TNF-α inhibitor, in patients with CRPS. CRPS patients treated with infliximab between January 2015 and January 2022 were approached to participate in this retrospective study. Medical records were screened for age, gender, medical history, CRPS duration, and CRPS severity score. Additionally, treatment effect, dose and duration, and side effects were extracted from medical records. Patients who still receive infliximab completed a short global perceived effect survey. Eighteen patients received infliximab, and all but two gave consent. Trial treatment with three sessions of 5 mg/kg intravenous infliximab was completed in 15 patients (93.7%). Eleven patients (73.3%) were categorized as responders with a positive treatment effect. Treatment was continued in nine patients, and seven patients are currently treated. Infliximab dose is 5 mg/kg, and frequency is every four to six weeks. Seven patients completed a global perceived effect survey. All patients reported improvement (median 2, IQR 1-2) and treatment satisfaction (median 1, IQR 1-2). One patient described side effects such as itching and rash. Infliximab proved effective in 11 out of 15 CRPS patients. Seven patients are still being treated. Further research is needed on the role of infliximab in the treatment of CRPS and possible predictors of response to treatment.

ID: 217192 CRPS Successfully Managed With Peripheral Nerve Stimulation: A Case Report

Complex Regional Pain Syndrome (CRPS) is characterized by prolonged and greater than expected pain, typically following a traumatic injury. [1] CRPS is commonly diagnosed using the Budapest criteria; however, there is no universally accepted treatment regimen available to patients with the condition. [2] The treatment of CRPS requires a multicomponent approach, including patient education, behavioral modification, physical therapy, medical therapy, and potentially interventional procedures.

Ketamine for Complex Regional Pain Syndrome: A Narrative Review Highlighting Dosing Practices and Treatment Response.

This is a narrative review of intravenous ketamine infusions for the treatment of complex regional pain syndrome (CRPS). It briefly covers the definition of CRPS, its epidemiology, and other treatments before introducing ketamine as the article's focus. A summary of ketamine's evidence base and its mechanisms of action is provided. The authors then review ketamine dosages reported in peer-reviewed literature for the treatment of CRPS, and their associated duration of pain relief. The observed response rates to ketamine and predictors of treatment response are also discussed.

A comparison of analgesic efficacy and safety of clonidine and methylprednisolone as additives to 0.25% ropivacaine in stellate ganglion block for the treatment of complex regional pain syndrome: a prospective randomised single blind study.

The role of the sympathetic nervous system appears to be central in causing pain in complex regional pain syndrome (CRPS). The stellate ganglion block (SGB) using additives with local anesthetics is an established treatment modality. However, literature is sparse in support of selective benefits of different additives for SGB. Hence, the authors aimed to compare the efficacy and safety of clonidine with methylprednisolone as additives to ropivacaine in the SGB for treatment of CRPS. A prospective randomized single blinded study (the investigator blinded to the study groups) was conducted among patients with CRPS-I of the upper limb, aged 18-70 years with American Society of Anaesthesiologists physical status I-III. Clonidine (15 μg) and methylprednisolone (40 mg) were compared as additives to 0.25% ropivacaine (5 mL) for SGB. After medical treatment for two weeks, patients in each of the two groups were given seven ultrasound guided SGBs on alternate days. There was no significant difference between the two groups with respect to visual analogue scale score, edema, or overall patient satisfaction. After 1.5 months follow-up, however, the group that received methylprednisolone had better improvement in range of motion. No significant side effects were seen with either drug. The use of additives, both methylprednisolone and clonidine, is safe and effective for the SGB in CRPS. The significantly better improvement in joint mobility with methylprednisolone suggests that it should be considered promising as an additive to local anaesthetics when joint mobility is the concern.

Stellate ganglion block beyond chronic pain: A literature review on its application in painful and non-painful conditions

Abstract Cervical sympathetic or stellate ganglion blocks (SGBs) have been commonly used in the treatment of painful conditions like complex regional pain syndrome (CRPS). However, there is literature to suggest its utility in managing non-painful conditions as well. The focus of this literature review is to provide an overview of indications for SGB for painful and non-painful conditions. We identified published journal articles in the past 25 years from Embase and PubMed databases with the keywords “cervical sympathetic block, stellate ganglion blocks, cervical sympathetic chain, and cervical sympathetic trunk”. A total of 1556 articles were obtained from a literature search among which 311 articles were reviewed. Among painful conditions, there is a lack of evidence in favor of or against the use of SGB for CRPS despite its common use. SGB can provide postoperative analgesia in selective surgeries and can be effective in temporary pain control of refractory angina and the acute phase of herpes zoster infection. Among non-painful conditions, SGB may have beneficial effects on the management of post-traumatic stress disorder (PTSD), refractory ventricular arrhythmias, hot flashes in postmenopausal women, and breast cancer–related lymphedema. Additionally, there have been various case reports illustrating the benefits of SGB in the management of cerebral vasospasm, upper limb erythromelalgia, thalamic and central post-stroke pain, palmar hyperhidrosis, orofacial pain, etc. In our review of literature, we found that SGB can be useful in the management of various non-painful conditions beyond the well-known treatment for CRPS, although further studies are required to prove its efficacy.

Modern Principles of Diagnosis and Treatment in Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is a relatively common complication, occurring in 5% of cases after injury or surgery, particularly in the limbs. The incidence of CPRS is around 5- 26/100 000. The latest revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) now categorizes CRPS as a primary pain condition of multifactorial origin, rather than a disease of the skeletal system or the autonomic nervous system. Based on a selective search of the literature, we summarize current principles for the diagnosis and treatment of CRPS. Regional findings in CRPS are accompanied by systemic symptoms, especially by neurocognitive disorders of body perception and of symptom processing. The therapeutic focus is shifting from predominantly passive peripheral measures to early active treatments acting both centrally and peripherally. The treatment is centered on physiotherapy and occupational therapy to improve sensory perception, strength, (fine) motor skills, and sensorimotor integration/ body perception. This is supported by stepped psychological interventions to reduce anxiety and avoidance behavior, medication to decrease inflammation and pain, passive physical measures for reduction of edema and of pain, and medical aids to improve functioning in daily life. Interventional procedures should be limited to exceptional cases and only be performed in specialized centers. Spinal cord and dorsal root ganglion stimulation, respectively, are the interventions with the best evidence. The modern principles for the diagnosis and treatment of CRPS consider both, physiological and psychological mechanisms, with the primary goal of restoring function and participation. More research is needed to strengthen the evidence base in this field.

Outcome of Spinal Cord Stimulation for Complex Regional Pain Syndrome (CRPS): Real

Complex Regional Pain Syndrome (CRPS) is often refractory to conventional pain therapies. Spinal cord stimulation (SCS) has been proposed as an effective treatment for refractory CRPS. We present here analysis of data from patients with refractory CRPS who underwent SCS trials and implants from July 2017 to 28 February 2022 in our program.

Cervical dorsal root ganglion stimulation for complex regional pain syndrome: Technical description and results of seven cases.

Complex regional pain syndrome (CRPS) is characterized by nociplastic pain with alterations in sympathetic function. Neuromodulation could be a useful alternative therapy option. Dorsal root ganglion (DRG) stimulation has demonstrated better results than conventional spinal cord stimulation (SCS) for patients with CRPS in lower limbs. We report a case series of seven patients treated with cervical DRG stimulation for CRPS of the hand that required neuromodulation for pain relief, after no response with other analgesic techniques (medication and interventional). We report retrospective data collection of seven consecutive patients with a 1-year follow-up. Seven patients were trialed, and six were implanted with a permanent pulse generator after achieving more than 50% pain relief during 2-7 days of trial phase. The average pain relief (rated on a standard 100 mm visual analog scale) after 1 year of treatment was 64.3% ± 16.6. No major complications were observed during a 1-year follow-up. The results for cervical DRG stimulation are similar to other DRG stimulation studies for the treatment of refractory CRPS at lower levels. The cervical DRG implant technique guided with C-arm fluoroscopy and under conscious sedation could be a safe and effective option for relieving pain of the upper limbs CRPS. Monitoring neural status is required for cervical DRG stimulation either with a responder awake patient or with intraoperative neural monitoring in non-responder patients.

Pharmacologic Treatments in Upper Extremity Complex Regional Pain Syndrome: A Review and Analysis of Quality of Evidence.

The purpose of this study was to assess the quality of evidence informing on common pharmacologic modalities used in upper extremity complex regional pain syndrome (CRPS). A literature search was performed for primary prospective trials that reported on the pharmacologic treatment of CRPS type I and II specific to the upper extremity. Thirty-one trials were included and evaluated by 2 independent reviewers according to the Oxford Levels of Evidence (LOE), modified Coleman Methodology Score, and the revised Consolidated Standards of Reporting Trials (CONSORT) score. Cohen's kappa coefficient was calculated to measure interrater reliability. Twenty-two Oxford LOE I and 9 level II trials met the inclusion criteria. Overall, there was high interrater reliability in the Oxford LOE (100% agreement), modified Coleman Methodology Score (87% agreement), and CONSORT score (94% agreement). The pharmacologic interventions with the highest quality of evidence supporting use in treatment of upper extremity CRPS were bisphosphonates and ketamine. Interventions that lack high-quality evidence are tricyclic antidepressants (TCAs) and topical dimethyl sulfoxide (DMSO). Pharmacologic agents that remain inconclusive are calcitonin, gabapentin, mycophenolate, probiotics, steroids, nonsteroidal anti-inflammatory drugs, vitamin C, and N-acetylcysteine. Agents with limited benefit are mannitol, isosorbide dinitrate, guanethidine, and morphine. Based on the evidence evaluated in this study, bisphosphonates should be considered as a first-line medication in the treatment of CRPS. In patients presenting with chronic or refractory CRPS, strong consideration should be given for the use of ketamine. Adjunct treatment in the acute setting should include TCAs and/or topical DMSO.

TREATMENT MODALITIES OF COMPLEX REGIONAL PAIN SYNDROME AFTER HAND SURGERY A SYSTEMATIC REVIEW AND META-ANALYSIS STUDY

Background: complex regional pain syndrome is a complex medical condition. Physical/occupational treatments, psychiatric counseling, neuropathic pain medicines, anti-inflammatories, and surgical intervention are utilized to treat complex regional pain syndrome (CRPS).

Combining Stellate ganglion block and intravenous regional anesthesia to treat complex regional pain syndrome: A 19-years' experience in a tertiary center.

To study reduction in pain score after treatment with intravenous regional anesthesia (IVRA) and Stellate ganglion block (SGB) combination on complex regional pain syndrome (CPRS) patients and to quantify patients' satisfaction with treatment and occurrence of complications. This is a record-based retrospective review carried out in 2020, targeting patients treated in the University of Jordan Hospital, Amman, Jordan, over the years 2002-2020. Among 99 patients, a significant drop in pain scores occurred in 88% of the patients' sample. Gender, age, type of CRPS, and duration of symptoms didn't affect statistical results. An average of 8.6 sessions needed to achieve 50% drop in pain score, and 2-3 sessions for first clinical improvement. Patients with previous application of plaster of Paris had increased success rates. We find it practical, inexpensive, safe, and straightforward to combine SGB with IVRA for CRPS patients.