Shifting brain circuits in pain chronicity.

The evaluation of brain changes to a specific pain condition in pediatric and adult patients allows for insights into potential mechanisms of pain chronicity and possibly long-term brain changes. Here we focused on the primary somatosensory system (SS) involved in pain processing, namely the ventroposterolateral thalamus (VPL) and the primary somatosensory cortex (SI). We evaluated, using MRI, three specific processes: (a) somatotopy of changes in the SS for different pain origins (viz., foot vs. arm); (b) differences in acute (ankle sprain versus complex regional pain syndrome-CRPS); and (c) differences of the effects of CRPS on SS in pediatric versus adult patients. In all cases, age- and sex-matched individuals were used as controls. Our results suggest a shift in concurrent gray matter density (GMD) and resting functional connectivity strengths (rFC) across pediatric and adult CRPS with (a) differential patterns of GMD (VPL) and rFC (SI) on SS in pediatric vs. adult patterns that are consistent with upper and lower limb somatotopical organization; and (b) widespread GMD alterations in pediatric CRPS from sensory, emotional and descending modulatory processes to more confined sensory-emotional changes in adult CRPS and rFC patterns from sensory-sensory alterations in pediatric populations to a sensory-emotional change in adult populations. These results support the idea that pediatric and adult CRPS are differentially represented and may reflect underlying differences in pain chronification across age groups that may contribute to the well-known differences between child and adult pain vulnerability and resilience.

The Effectiveness of Fluidotherapy in Poststroke Complex Regional Pain Syndrome: A Randomized Controlled Study.

OBJECTIVE: To evaluate whether combining fluidotherapy to conventional rehabilitation program provides additional improvements on pain severity, upper extremity functions, and edema volume in patients with poststroke complex regional pain syndrome (CRPS). DESIGN: Randomized controlled trial. SETTING: Training and research hospital. PARTICIPANTS: Thirty hemiplegic patients with subacute stage CRPS type-1 of the upper extremity. INTERVENTIONS: The patients randomly divided into 2 groups. Both groups received a 3 week conventional rehabilitation program (5 days/week, 2-4 hours/day). Experimental group received 15 sessions additional fluidotherapy application to the affected upper extremity (40 °C, 20 minutes in continuous mode, 5 sessions/week). MAIN OUTCOME MEASURES: We evaluated the distal upper arm edema with a volumeter. Other used clinical assessment scales were Brunnstrom recovery stages of the arm and hand for motor recovery, motor items of the functional independence measure for functional status, visual analog scale for pain severity, and the painDETECT questionnaire for presence and the severity of neuropathic pain. RESULTS: The mean age of the participants was 64.3 ± 11.66 (28-84). At the post-treatment evaluation, significant improvements were revealed regarding to the edema volume, pain visual analog scale, painDETECT and functional independence measure scores, and the Brunnstrom stages of upper extremity and hand in both groups (P < .05). But among the parameters mentioned above, only the decrease in edema volume and the painDETECT scores were greater in fluidotherapy group than the control group (P < .05). CONCLUSIONS: Addition of the fluidotherapy to the conventional rehabilitation program provides better improvements on neuropathic pain and edema volume in subacute stage poststroke CRPS.

Electroacupuncture for Reflex Sympathetic Dystrophy after Stroke: A Meta-Analysis.

BACKGROUND: Reflex sympathetic dystrophy (RSD) is the common complication among stroke and cerebral injury patients, which is lack of safe and effective treatment. Electroacupuncture (EA) may potentially be a reliably therapy, but the evidence is insufficiency. METHODS: Cochrane Library, MEDLINE, Embase, Chinese National Knowledge Infrastructure, Wan Fang Data, the Chinese Biology Medicine disc, etc., were searched, until July 20, 2018. We included random control trials that contrast EA with conventional rehabilitation therapy for the treatment of RSD. Main outcomes were visual analog scale score and Fugl-Meyer upper limb motor function scoring scale, other outcomes such as Barthel index, and hand swelling score were also collected. Data in included studies were extracted into an excel and pooled by Stata/MP 14.1. RESULTS: We incorporated 13 studies involving 1040 RSD patients and outcomes were from 2 to 6 weeks' follow-up. The analgesic effect between 2 groups had statistically significant difference (weighted mean difference [WMD] = -1.122, 95% confidence interval [CI] [-1.682 to -.562], P = .000], a statistical difference existed in improving dysfunction between 2 groups: (WMD = 6.039, 95% CI [2.231-.916], P = .000). EA groups had a better effect on improving activities of daily life abilities (WMD = 12.170, 95% CI [6.657-17.682], P < .00011] and better detumescence effect (WMD = -.800, 95% CI [-1.972 to -.212], P = .000] contrast to conventional rehabilitation therapy. CONCLUSIONS: This meta-analysis supports that EA has a positive effect on alleviating pain, improving limb dysfunction, and promoting activities of daily living. On account of moderate-quality random control trials and high heterogeneity, further high-quality studies are imperative to optimize the EA treatment program.

Physical therapy under hypnosis for the treatment of patients with type 1 complex regional pain syndrome of the hand and wrist: Retrospective study of 20 cases.

Type 1 complex regional painful syndrome (CRPS-1) has a complex physiopathology. The aim of this study was to evaluate the effectiveness of physical therapy under hypnotherapy to treat this condition. Twenty patients with CRPS-1 at the wrist and hand were evaluated retrospectively: 13 women and 7 men with an average age of 56 years (34-75). Thirteen patients were in the inflammatory phase and 7 in the dystrophic phase. The main endpoints were pain (VAS, analgesic use), stiffness (wrist and finger range of motion), and strength (pinch and grasp). Secondary endpoints were functional scores (QuickDASH, PWRE), patient satisfaction, return to work, and side effects. Results were satisfactory in all cases after 5.4 sessions on average. VAS decreased by 4 points, PWRE-pain by 4.1 points, and analgesic use was limited to paracetamol upon request. Finger and wrist range of motion increased and the QuickDASH decreased by 34 points, PRWE-function by 3.8 points, pinch strength increased 4 points, and grasp strength by 10 points. Return to work was possible in 80% of the cases. All patients were satisfied or very satisfied with the treatment. Physical therapy under hypnosis appears to be an effective treatment for CRPS-1 at the wrist and hand no matter the etiology.

Sympathomimetic amine therapy found effective for treatment of refractory chronic complex regional pain syndrome (reflex sympathetic dystrophy).

PURPOSE: To determine if treatment with sympathomimetic amines could improve the pain from complex regional pain disorder (CRPD) which was keeping a woman from trying to conceive her second child. MATERIALS AND METHODS: Dextroamphetamine sulfate was prescribed. RESULTS: Within a short length of time the woman's wrist pain considerably improved to the point that she is ready to try in vitro fertilization once again to have a second baby. CONCLUSIONS: Though sympathomimetic amines are used by some reproductive endocrinologists for unexplained infertility and unexplained recurrent miscarriages, the most common use by the gynecologist is for pelvic pain. Despite the thought by some clinicians and researchers that the etiology for CRPD may be related to sympathetic nervous system hyperactivity (and thus sympathomimetic amines could theoretically exacerbate the symptoms), in fact, the treatment with dextroamphetamine sulfate may turn out to be a new and possibly the most effective, least risky, and least expensive treatment to date for CRPD.

Multimodal physical therapy management of a 48-year-old female with post-stroke complex regional pain syndrome.

This case report describes a 48-year-old female who presented with complaints of right shoulder pain, hyperesthesias and swelling of the hand along with added symptoms of pain centralization following a cerebrovascular accident. On clinical evaluation, the patient satisfied the Budapest diagnostic criteria for Complex Regional Pain Syndrome (CRPS) type-1. Physical therapy management (1st three sessions) was initially focused on pain neurophysiology education with an aim to reduce kinesiophobia and reconceptualise her pain perception. The patient had an immediate significant improvement in her pain and functional status. Following this, pain modulation in the form of transcutaneous electrical nerve stimulation, kinesio tape application, "pain exposure" physical therapy and exercise therapy was carried out for a period of 7 weeks. The patient had complete resolution of her symptoms which was maintained at a six-month follow-up.

Graded motor imagery and the impact on pain processing in a case of CRPS.

OBJECTIVE: Graded motor imagery (GMI) shows promising results for patients with complex regional pain syndrome (CRPS). METHODS: In a case with chronic unilateral CRPS type I, we applied GMI for 6 weeks and recorded clinical parameters and cerebral activation using functional magnetic resonance imaging (fMRI; pre-GMI, after each GMI block, and after 6 mo). Changes in fMRI activity were mapped during movement execution in areas associated with pain processing. A healthy participant served as a control for habituation effects. RESULTS: Pain intensity decreased over the course of GMI, and relief was maintained at follow-up. fMRI during movement execution revealed marked changes in S1 and S2 (areas of discriminative pain processing), which seemed to be associated with pain reduction, but none in the anterior insula and the anterior cingulate cortex (areas of affective pain processing). After mental rotation training, the activation intensity of the posterior parietal cortex was reduced to one third. DISCUSSION: Our case report develops a design capable of differentiating cerebral changes associated with behavioral therapy of CRPS type I study.

Modified graded motor imagery for complex regional pain syndrome type 1 of the upper extremity in the acute phase: a patient series.

Complex regional pain syndrome (CRPS) is a pathologic condition in which the painful experience is disproportionate in time and intensity in comparison with the inciting event. At present, the pathophysiology of CRPS is not well understood. Several studies have indicated that cortical reorganization plays a role in the persistence of the symptoms. A new promising approach, graded motor imagery (GMI), seems to be effective, but there are limited data for the CRPS-1 upper extremity population. The aim of this study was to demonstrate the effectiveness of a modified GMI (mGMI) protocol based on the work of Moseley to reduce pain and enhance functional capacities for a population with nonchronic CRPS-1 of the upper extremity. The following outcome measures were used to assess the clinical effectiveness: pain (short form of the McGill Pain Questionnaire), grip force (Martin vigorimeter), perception of upper extremity function (Disabilities of the Arm, Shoulder and Hand Questionnaire), and patient's global impression of change. All outcomes at T4 were compared with the baseline data (T0) using the Mann-Whitney test and the χ test (nonparametric tests). Seven patients were recruited for the study. At the end of the mGMI (T4), we obtained significant results for the decrease in the pain experienced in the last 7 days (visual analog scale; P=0.046), improvement in the affected extremity grip force (P=0.042), and the patient's global impression of change (P=0.015). However, the data of the perception of upper extremity function (Disabilities of the Arm, Shoulder and Hand Questionnaire) were not clinically or statistically significant. Our results indicate that this mGMI protocol seems to be a promising therapeutic modality to reduce pain. However, more investigations are needed to determine whether mGMI has a significant impact on upper extremity function.

Hypothalamic-pituitary-adrenal axis function in patients with complex regional pain syndrome type 1.

An exaggerated inflammatory process is considered an important pathophysiological feature of complex regional pain syndrome type 1 (CRPS-1). The hypothalamic-pituitary-adrenal (HPA) axis serves as a negative feedback mechanism for inflammatory processes. The present study examined the HPA axis function in patients with CRPS-1 by a determination of cortisol concentrations in saliva. Three sets of saliva samples were sequentially collected from 24 patients with CRPS-1 during medication (on-Med), 72 h after stopping medication (off-Med) and 8h after the oral administration of 1mg dexamethasone. One set of saliva samples was collected from healthy controls. The cortisol awakening response (CAR) and diurnal cortisol decline (DCD) were used as indices for HPA axis function. Cortisol levels during the post-awakening period in patients were increased following withdrawal of medications. The CAR during the off-Med condition was disappeared after administration of dexamethasone. Among the examined CRPS-related numerical variables, the frequency of spontaneous pain attacks showed relationships with the indices of HPA axis function. After classifying the patients into two subgroups, we observed that the CAR and DCD in patient who had a relatively high frequency of spontaneous pain attacks (subgroup 5 ≤) were lower and less steep than those in patient who had a relatively low frequency of spontaneous pain attacks (subgroup 0-4) for the on- and off-Med conditions. The CAR and DCD in subgroup 5 ≤ during their off-Med condition were comparable to those in controls. These results suggest that the increase in frequency of spontaneous pain attacks is associated with a reduced CAR and flattened DCD in patients CRPS-1.

Spinal cord stimulation in complex regional pain syndrome type I of less than 12-month duration.

INTRODUCTION: Complex regional pain syndrome type 1 (CRPS-1) has a 31% probability of becoming chronic. The early use of spinal cord stimulation (SCS) has been recommended as a strategy to prevent chronicity and functional impairment. METHODS: In a prospective study, we treated 74 CRPS-1 patients with a mean disease duration of 17 weeks with standard therapy consisting of physical therapy, topical dimethyl sulfoxide, analgesics, transcutaneous stimulation, and sympathetic blockade. Patients who did not respond to standard therapy were offered a treatment with SCS. In these patients, we investigated the impact on pain, quality of life, and function. RESULTS: Out of these 74 patients treated with standard therapy, six patients were included for early SCS treatment. The overall mean pain relief after one year was 35%. The mental component of the Short Form 36 improved; however, there was no effect on the physical component. None of the SCS treated patients showed a clear improvement in functional outcome. DISCUSSION: We conclude that the feasibility of performing a randomized controlled trial on early SCS therapy in CRPS-1 is low because of the good disease improvement with standard therapy in the first year after onset. This study raises questions about the need to use SCS early in the course of CRPS-1 because of the probable lack of additional benefit compared with SCS in chronic CRPS-1.

Complex regional pain syndrome following transfemoral catheterization.

Complex regional pain syndrome (CRPS) (previously reflex sympathetic dystrophy) is a chronic pain condition usually resulting as a consequence of trauma or surgery. Though described occasionally after vascular surgery, it is distinctly rare after percutaneous cardiovascular procedures. We report a case of CRPS following trans- femoral catheterization-related groin pseudoaneurysm. To our knowledge, this is the first such report following transfemoral catheterization. A 36-year-old female underwent an electrophysiological study and AV node re-entry tachycardia ablation using the left femoral vein approach. One month later she presented complaining of numbness and tingling in her left foot with swelling and mild groin discomfort. A lower extremity duplex scan showed a left common femoral artery pseudoaneurysm that was partially thrombosed and subsequently resolved spontaneously. The patient had intractable symptoms of pain, temperature changes, color changes, and trophic changes of the left foot. Conventional angiography was done to rule out occlusive arterial disease but just showed very sluggish flow. Further evaluation with transcutaneous oxymetry and 3-phase bone scan was consistent with microvascular dysfunction and poor cutaneous blood flow suggestive of cold-type CRPS. In this case report, we also review the clinical features and the vascular changes associated with CRPS and discuss the pathophysiology of the syndrome from a cardiovascular specialist's perspective. Interventionalists should be aware that CRPS is a possible, albeit rare, condition that may follow many vascular procedures that they perform on a daily basis.

Spinal cord stimulation is effective in management of complex regional pain syndrome I: fact or fiction.

BACKGROUND: Complex regional pain syndrome (CRPS) I is a debilitating neuropathic pain disorder characterized by burning pain and allodynia. Spinal cord stimulation (SCS) is effective in the treatment of CRPS I in the medium term but its long-term efficacy and ability to improve functional status remains controversial. OBJECTIVE: To evaluate the ability of SCS to improve pain, functional status, and quality of life in the long term. METHODS: We retrospectively analyzed 25 patients over a mean follow-up period of 88 months. The parameters for evaluation were visual analog scale (VAS), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI), EuroQoL-5D (EQ-5D) and Short Form 36 (SF-36), and drug consumption. Evaluations were conducted at point of entry, 3 months, 12 months, and last follow-up at 88 months (mean). RESULTS: At baseline, the mean scores were VAS 8.4, ODI 70%, BDI 28, EQ-5D 0.30, and SF-36 24. In general, maximum improvement was recorded at follow-up at 3 months (VAS 4.8, ODI 45%, BDI 15, EQ-5D 0.57, and SF-36 45). At last follow-up, scores were 5.6, 50%, 19, 0.57, and 40, respectively. Despite some regression, at last follow-up benefits were maintained and found to be statistically significant (P < .001) compared with baseline. Medication usage declined. SCS did not prevent disease spread to other limbs. Best results were achieved in stage I CRPS I, patients under 40 years of age, and those receiving SCS within 1 year of disease onset. CONCLUSION: SCS improves pain, quality of life, and functional status over the long term and consequently merits early consideration in the treatment continuum.

Abnormal thalamocortical activity in patients with Complex Regional Pain Syndrome (CRPS) type I.

Complex Regional Pain Syndrome (CRPS) is a neuropathic disease that presents a continuing challenge in terms of pathophysiology, diagnosis, and treatment. Recent studies of neuropathic pain, in both animals and patients, have established a direct relationship between abnormal thalamic rhythmicity related to Thalamo-cortical Dysrhythmia (TCD) and the occurrence of central pain. Here, this relationship has been examined using magneto-encephalographic (MEG) imaging in CRPS Type I, characterized by the absence of nerve lesions. The study addresses spontaneous MEG activity from 13 awake, adult patients (2 men, 11 women; age 15-62), with CRPS Type I of one extremity (duration range: 3months to 10years) and from 13 control subjects. All CRPS I patients demonstrated peaks in power spectrum in the delta (<4Hz) and/or theta (4-9Hz) frequency ranges resulting in a characteristically increased spectral power in those ranges when compared to control subjects. The localization of such abnormal activity, implemented using independent component analysis (ICA) of the sensor data, showed delta and/or theta range activity localized to the somatosensory cortex corresponding to the pain localization, and to orbitofrontal-temporal cortices related to the affective pain perception. Indeed, CRPS Type I patients presented abnormal brain activity typical of TCD, which has both diagnostic value indicating a central origin for this ailment and a potential treatment interest involving pharmacological and electrical stimulation therapies.

A severe case of complex regional pain syndrome I (reflex sympathetic dystrophy) managed with spinal cord stimulation.

Complex regional pain syndrome is a condition that usually affects the upper or lower extremities. The cause is not clearly understood. We report a case of a severe form of a rapidly progressive complex regional pain syndrome type I developing after a right shoulder injury managed with spinal cord stimulation (SCS). After failed conservative treatments, a rechargeable SCS system was implanted in the cervical spine. Allodynia and dystonia improved but the patient subsequently developed similar symptoms in lower right extremity followed by her lower left extremity. The patient became wheelchair bound. A second rechargeable SCS with a paddle electrode was implanted for the lower extremity coverage. The patient's allodynia and skin lesions improved significantly. However, over time, her initial symptoms reappeared which included skin breakdown. Due to the need for frequent recharging, the system was removed. During explantation of the surgical paddle lead, it was noted by the neurosurgeon that the contacts of the paddle lead were detached from the lead. After successful implantation of another SCS system, the patient was able to reduce her medications and is now able to ambulate with the use of a left elbow crutch.

Spinal cord stimulation: "neural switch" in complex regional pain syndrome type I.

INTRODUCTION: Complex regional pain syndrome type I (CRPS I) is a neuropathic pain disorder of unclear etiology. It commonly follows a trivial injury and is characterized by spontaneous pain manifesting regionally that is disproportionate to the inciting event. Associated signs and symptoms include allodynia, hyperalgesia, edema, sudomotor, vasomotor abnormalities, and trophic changes. Although multiple modalities exist to treat CRPS I, significant disability, diminution in quality of life, and reduction in overall health often accompany the syndrome. CASE: A case of a 57-year-old man with CRPS I who was treated with spinal cord stimulation (SCS) after failing conservative therapy is presented. One month following treatment, he experienced complete symptom resolution such that stimulation was subsequently discontinued without recurrence over the 1-year follow-up period. CONCLUSIONS: To date there is currently no reliably validated "cure" for CRPS. There has only been one recent report where SCS resulted in the complete eradication of the signs and symptoms associated with CRPS. This series involved adolescent girls aged 11-14 years of age, who tend to have a more benign and self-limited treatment course than that seen in adults. This raises the question as to whether a "neural switch" exists, and if so, where it is located. We postulate that the inter-neuronal connections between the central and peripheral nervous systems implicated by the current pathophysiological model is the most plausible site of this "neural switch," and that reorganization of this interface can account for the ability of SCS to effect a complete "cure" in CRPS.

The efficacy of manual lymphatic drainage therapy in the management of limb edema secondary to reflex sympathetic dystrophy.

The objective of this study is to investigate the efficacy of manual lymphatic drainage (MLD) therapy in edema secondary to the reflex sympathetic dystrophy (RSD). A total of 34 patients were allocated randomly into two groups. All of the patients undertook nonstreoidal anti-inflammatory drug, physical therapy and therapeutic exercise program for 3 weeks. Patients in study group undertook MLD therapy additionally. Then the patients continued 2-month maintenance period with recommended home programs. Volumetric measurements pain scores and functional measurements were assessed at baseline, after treatment and 2 months after the treatment. After treatment, improvement in edema was statistically significant in the study group but not in the control group. At follow-up, with respect to baseline, improvements were not significant in both of the groups. Between the groups, difference of the percentage improvements in edema was statistically significant with superiority of MLD group after treatment, but not significant at follow-up. In this pilot study, MLD therapy was found to be beneficial in the management of edema resulted from RSD. Although the long-term results showed tendency towards improvement, the difference was not significant.

Does evidence support physiotherapy management of adult Complex Regional Pain Syndrome Type One? A systematic review.

OBJECTIVE: To source and critically evaluate the evidence on the effectiveness of Physiotherapy to manage adult CRPS-1. DESIGN: Systematic literature review. METHODS: Electronic databases, conference proceedings, clinical guidelines and text books were searched for quantitative studies on CRPS-1 in adults where Physiotherapy was a sole or significant component of the intervention. Data were extracted according to predefined criteria by two independent reviewers. Methodological quality was assessed using the Critical Review Form. RESULTS: The search strategy identified 1320 potential articles. Of these, 14 articles, representing 11 studies, met inclusion criteria. There were five randomised controlled trials, one comparative study and five case series. Methodological quality was dependent on study type, with randomised controlled trials being higher in quality. Physiotherapy treatments varied between studies and were often provided in combination with medical management. This did not allow for the 'stand-alone' value of Physiotherapy to be determined. Heterogeneity across the studies, with respect to participants, interventions evaluated and outcome measures used, prevented meta-analysis. Narrative synthesis of the results, based on effect size, found there was good to very good quality level II evidence that graded motor imagery is effective in reducing pain in adults with CRPS-1, irrespective of the outcome measure used. No evidence was found to support treatments frequently recommended in clinical guidelines, such as stress loading. CONCLUSIONS: Graded motor imagery should be used to reduce pain in adult CRPS-1 patients. Further, the results of this review should be used to update CRPS-1 clinical guidelines.