Socioeconomic Disparities in the Utilization of Spinal Cord Stimulation Therapy in Patients with Chronic Pain.

OBJECTIVES: Spinal cord stimulation (SCS) therapies are used in the management of patients with complex regional pain syndrome I (CRPS I) and failed back surgery syndrome (FBSS). The purpose of this study was to investigate the racial and health insurance inequalities with SCS therapy in patients with chronic pain who had CRPS I and FBSS. METHODS: Patients with chronic pain who had a discharge diagnosis of FBSS and CRPS I were identified using the National Inpatient Sample database. Our primary outcome was defined as the history of SCS utilization by race/ethnicity, income quartile, and insurance status. Multivariable logistic regression was used to determine the variables associated with utilization of SCS therapy. RESULTS: Between 2011 and 2015, 40,858 patients who were hospitalized with a primary diagnosis of FBSS and/or CRPS I were identified. Of these patients, 1,082 (2.7%) had a history of SCS therapy. Multivariable regression analysis revealed that compared to White patients, Black and Hispanic patients had higher odds of having SCS therapy (Black patients: odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.12 to 1.77; P = 0.003; Hispanic patients: OR = 1.41; 95% CI, 1.10 to 1.81; P = 0.007). Patients with private insurance had significantly higher odds of having SCS therapy compared with those with Medicare (OR = 1.24; 95% CI, 1.08 to 1.43; P = 0.003). Compared to patients with Medicare, Medicaid patients had lower odds of having SCS therapy (OR = 0.50; 95% CI, 0.36 to 0.70; P < 0.001). CONCLUSIONS: Our study suggests that socioeconomic disparities may exist in the utilization of SCS among hospitalized patients with CRPS I and FBSS the United States. However, confirming these data from other administrative databases, in the outpatient setting, may shed more insight.

Perioperative Management of a Parturient with Complex Regional Pain Syndrome for Elective C-Section.

A 33 year-old female at 38 weeks gestation with a history of Complex Regional Pain Syndrome (CRPS) Type 1 of the upper extremities, diagnosed 13 years prior to this admission, was scheduled for an elective cesarean section (C-Section). She refused neuraxial anesthesia and requested general anesthesia. This abstract discusses the general anesthesia steps taken to pre-empt recurrence of CRPS symptoms.

Activation of cannabinoid receptor 2 attenuates mechanical allodynia and neuroinflammatory responses in a chronic post-ischemic pain model of complex regional pain syndrome type I in rats.

Complex regional pain syndrome type 1 (CRPS-I) remains one of the most clinically challenging neuropathic pain syndromes and its mechanism has not been fully characterized. Cannabinoid receptor 2 (CB2) has emerged as a promising target for treating different neuropathic pain syndromes. In neuropathic pain models, activated microglia expressing CB2 receptors are seen in the spinal cord. Chemokine fractalkine receptor (CX3CR1) plays a substantial role in microglial activation and neuroinflammation. We hypothesized that a CB2 agonist could modulate neuroinflammation and neuropathic pain in an ischemia model of CRPS by regulating CB2 and CX3CR1 signaling. We used chronic post-ischemia pain (CPIP) as a model of CRPS-I. Rats in the CPIP group exhibited significant hyperemia and edema of the ischemic hindpaw and spontaneous pain behaviors (hindpaw shaking and licking). Intraperitoneal administration of MDA7 (a selective CB2 agonist) attenuated mechanical allodynia induced by CPIP. MDA7 treatment was found to interfere with early events in the CRPS-I neuroinflammatory response by suppressing peripheral edema, spinal microglial activation and expression of CX3CR1 and CB2 receptors on the microglia in the spinal cord. MDA7 also mitigated the loss of intraepidermal nerve fibers induced by CPIP. Neuroprotective effects of MDA7 were blocked by a CB2 antagonist, AM630. Our findings suggest that MDA7, a novel CB2 agonist, may offer an innovative therapeutic approach for treating neuropathic symptoms and neuroinflammatory responses induced by CRPS-I in the setting of ischemia and reperfusion injury.

Effects of Mirror Therapy in Stroke Patients With Complex Regional Pain Syndrome Type 1: A Randomized Controlled Study.

OBJECTIVE: To investigate the effects of mirror therapy on upper limb motor functions, spasticity, and pain intensity in patients with hemiplegia accompanied by complex regional pain syndrome type 1. DESIGN: Randomized controlled trial. SETTING: Training and research hospital. PARTICIPANTS: Adult patients with first-time stroke and simultaneous complex regional pain syndrome type 1 of the upper extremity at the dystrophic stage (N=30). INTERVENTIONS: Both groups received a patient-specific conventional stroke rehabilitation program for 4 weeks, 5 d/wk, for 2 to 4 h/d. The mirror therapy group received an additional mirror therapy program for 30 min/d. MAIN OUTCOME MEASURES: We evaluated the scores of the Brunnstrom recovery stages of the arm and hand for motor recovery, wrist and hand subsections of the Fugl-Meyer Assessment (FMA) and motor items of the FIM-motor for functional status, Modified Ashworth Scale (MAS) for spasticity, and visual analog scale (VAS) for pain severity. RESULTS: After 4 weeks of rehabilitation, both groups had significant improvements in the FIM-motor and VAS scores compared with baseline scores. However, the scores improved more in the mirror therapy group than the control group (P<.001 and P=.03, respectively). Besides, the patients in the mirror therapy arm showed significant improvement in the Brunnstrom recovery stages and FMA scores (P<.05). No significant difference was found for MAS scores. CONCLUSIONS: In patients with stroke and simultaneous complex regional pain syndrome type 1, addition of mirror therapy to a conventional stroke rehabilitation program provides more improvement in motor functions of the upper limb and pain perception than conventional therapy without mirror therapy.

[Bone resorption in posttraumatic dystrophy. Root cause analysis based on the literature]. / Knochenresorption bei posttraumatischer Dystrophie. Ursachenanalyse anhand der Literatur.

BACKGROUND: In posttraumatic dystrophy the resorption of cancellous bone remains an unsolved phenomenon. OBJECTIVES: The possible effects of arteriovenous (av) anastomoses, hypoxia and acidosis in posttraumatic dystrophy on cancellous bone structures should be elucidated. MATERIAL AND METHODS: In posttraumatic dystrophy of the hand after distal radius fracture, hand fractures and elective hand surgery [20] the results suggest that persistent av anastomoses could be the reason for this syndrome. Possible pathways for the occurrence of cancellous bone resorption are discussed in context with the literature. RESULTS AND CONCLUSION: Intraosseous av anastomoses with acidosis and hypoxia of the tissues are probably responsible for the excessive activity of osteoclasts in acute posttraumatic dystrophy. Even enhancements in the late static phase of the three phase bone scan (TPBS) are in agreement with this hypothesis. In cancellous bone these enhancements are induced by the bone seeking tracers. The nomenclature for these tracer molecules is in line with the recommendations of International Union of Pure and Applied Chemistry (IUPAC) as methylene bisphosphonate and hydroxymethylene bisphosphonate. From this, therapeutic recommendations for posttraumatic dystrophy can be derived. The term diphosphonates should be changed to bisphosphonates.

Intravenous ketamine infusions for chronic algodystrophy: a review.

Abstract Chronic algodystrophy is difficult to treat, because the disease in this stage is usually resistant to many therapies. It particularly concerns conditions with predominant severe, intractable pain and disability of the involved extremity. In these, the severest cases, searching for effective pain control therapy is extremely important. Intravenous ketamine infusions constitute a promising therapy, which appeared recently. Ketamine possesses properties of blocking central sensitization and development of neuropathic pain through its effect on NMDA receptor, a critical factor in this process. The article presents problem of chronic, refractory algodystrophy, mechanism of ketamine action in pain control, literature review on treatment outcomes and authors' own experience in this field. Ketamine seems to be a useful option for pain control in patients with refractory algodystrophy.

Alpha-lipoic acid reduces nociception by reducing oxidative stress and neuroinflammation in a model of complex regional pain syndrome type I in mice.

Complex regional pain syndrome type I (CRPS-I) is a disabling pain condition without adequate treatment. Chronic post-ischemia pain injury (CPIP) is a model of CRPS-I that causes allodynia, spontaneous pain, inflammation, vascular injury, and oxidative stress formation. Antioxidants, such as alpha lipoic acid (ALA), have shown a therapeutic potential for CRPS-I pain control. Thus, we aim to evaluate if ALA repeated treatment modulates neuroinflammation in a model of CRPS-I in mice. We used male C57BL/6 mice to induce the CPIP model (O-ring torniquet for 2 h in the hindlimb). For the treatment with ALA or vehicle (Veh) mice were randomly separated in four groups and received 100 mg/kg orally once daily for 15 days (CPIP-ALA, CPIP-Veh, Control-ALA, and Control-Veh). We evaluated different behavioral tests including von Frey (mechanical stimulus), acetone (cold thermal stimulus), rotarod, open field, hind paw edema determination, and nest-building (spontaneous pain behavior). Also, hydrogen peroxide (H2O2) levels, NADPH oxidase and superoxide dismutase (SOD) activity in the sciatic nerve and spinal cord, and Iba1, Nrf2, and Gfap in spinal cord were evaluated at 16 days after CPIP or sham induction. Repeated ALA treatment reduced CPIP-induced mechanical and cold allodynia and restored nest-building capacity without causing locomotor or body weight alteration. ALA treatment reduced SOD and NADPH oxidase activity, and H2O2 production in the spinal cord and sciatic nerve. CPIP-induced neuroinflammation in the spinal cord was associated with astrocyte activation and elevated Nfr2, which were reduced by ALA. ALA repeated treatment prevents nociception by reducing oxidative stress and neuroinflammation in a model of CRPS-I in mice.

Anti tumor necrosis factor - alpha adalimumab for complex regional pain syndrome type 1 (CRPS-I): a case series.

BACKGROUND AND AIMS: Evidence suggests tumor necrosis factor-alpha (TNF-α) mediates, at least in part, symptoms and signs in complex regional pain syndrome (CRPS). Here, we present a case series of patients with CRPS type 1, in whom the response to the anti-TNF-α adalimumab was assessed. METHODS: Ten patients with CRPS type 1 were recruited. Assessments were performed before treatment, at 1 week, and 1, 3, and 6 months following 3 biweekly subcutaneous injections (40 mg/0.8 mL) adalimumab (Humira(®) ) and included the followings: Pain intensity using a 0-10 cm visual analog scale; the Short Form of the McGill Pain Questionnaire; the Beck Depression Inventory; the SF-36 questionnaire and mechanical and thermal thresholds (Von frey hair and Thermal Sensory Analyzer, respectively). In addition to the description of individual patient responses, both intention to treat (ITT) and per-protocol (PP) analyses were performed for the entire group. RESULTS: Three subgroups of patients were identified (3 patients in each): "nonresponders", "partial responders", and "robust responders" in whom improvement in almost all parameters was noted. Both the ITT and PP analyses demonstrated only a trend toward improvement in mechanical pain thresholds following treatment (ITT χ² = 13.83, P = 0.008; PP χ² = 10.29, P = 0.036). CONCLUSION: These results suggest adalimumab, and possibly other anti-TNF-α, can be potentially useful in some (although not in all) patients with CRPS type 1. These preliminary results along with the growing body of evidence which points to the involvement of TNF-α in the pathogenesis of CRPS justify further studies in this area.

Manual lymphatic drainage in management of edema in a case with CRPS: why the(y) wait?

Complex regional pain syndrome (CRPS) is a disorder characterized by pain, edema, skin color changes and autonomic abnormalities. Its treatment is quite difficult and in most of the patients effective results cannot be reached. Manual lymphatic drainage is a very rare method for managing limb edema in CRPS. In this case report, the dramatic response of an excessive edema to lymphatic drainage was discussed in a CRPS patient.

Regional migratory osteoporosis: case report of a patient with neuropathic pain.

Regional migratory osteoporosis (RMO) is an idiopathic disorder characterized by severe periarticular pain, transient and migratory arthralgia, and osteoporosis. Osteoporosis in this disease may appear in the form of local regional osteoporosis and bone marrow edema or generalized osteoporosis. It occurs most commonly in middle-aged men and late second or third trimester pregnant women. The laboratory findings of the disease are usually normal and do not demonstrate apparent anomalies. The presence of bone marrow edema on MRI is its characteristic finding. RMO can only be separated from transient osteoporosis of hip and avascular necrosis with migration to other joints. Clinically, RMO progresses in three stages: increasing pain and disability, radiological findings (osteopenia), maximalization of symptoms, and finally, the regression of the disease and radiological changes. In this case report, we present a 29-year-old woman whose symptoms had first appeared at the second trimester of pregnancy and migrated both to the other joints in the proximo-distal direction and to the adjacent bones within the same joint. She also had symptoms such as hyperalgesia, hyperesthesia and hypertrichosis along with neuropathic pain, which she described as a burning, biting, and prickling type of pain at the right leg. The neuropathic pain of the patient was resistant to medical treatment. We believe that this case was worth reporting because of the obstinate clinical course of the patient's disease and her severe neuropathic pain that was resistant to treatment.

Novel Presentation of Pediatric Complex Regional Pain Syndrome with Concurrent Chromhidrosis: A Case Report.

CASE: An 11-year-old female patient presented to our clinic with a low-grade lateral ankle sprain that was subsequently treated with a lace-up ankle brace. On the reintroduction of weight bearing, the patient developed recurrent ankle pain and symptoms consistent with complex regional pain syndrome (CRPS) Type 1. On physical examination, the patient was found to have a concurrent chromhidrosis in the injured area, which is a novel presentation of CRPS. CONCLUSION: Patients with CRPS found to have superficial skin discoloration should be evaluated further to investigate for chromhidrosis. Early diagnosis can improve the treatment of CRPS and allow for appropriate management of varying manifestations, such as chromhidrosis.

Translating the Dutch Walking Stairs, Walking Ability and Rising and Sitting Questionnaires into German and assessing their concurrent validity with VAS measures of pain and activities in daily living.

BACKGROUND: The Dutch Walking Stairs, Walking Ability and Rising and Sitting Questionnaires are three validated instruments to measure physical activity and limitations in daily living in patients with lower extremity disorders living at home of which no German equivalents are available. Our scope was to translate the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires into German and to verify its concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale. METHODS: We translated the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires according to published guidelines. Demographic data and validity were assessed in 52 consecutive patients with Complex Regional Pain Syndrome 1 of the lower extremity. Information on age, duration of symptoms, type of Complex Regional Pain Syndrome 1 and type of initiating event were obtained. We assessed the concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale. RESULTS: We found that variability in the German Walking Stairs, Walking Ability and Rising and Sitting Questionnaires was largely explained by measures of pain and activities in daily living on the Visual Analogue Scale. CONCLUSION: Our study shows that the domains pain and activities in daily living are properly represented in the German versions of the Walking Stairs, Walking Ability and Raising and Sitting Questionnaires. We would like to propagate their use in clinical practice and research alike.

Somatosensory conflicts in complex regional pain syndrome type 1 and fibromyalgia syndrome.

The somatosensory system is an integral component of the motor control system that facilitates the recognition of location and experience of peripheral stimuli, as well as body part position and differentiation. In chronic pain, this system may be disrupted by alterations in peripheral and cortical processing. Clinical symptoms that accompany such changes can be difficult for patients to describe and health care practitioners to comprehend. Patients with chronic pain conditions such as complex regional pain syndrome or fibromyalgia typically describe a diverse range of somatosensory changes. This article describes how sensory information processing can become disturbed in fibromyalgia syndrome and complex regional pain syndrome and how symptoms can potentially be explained by the mechanisms that generate them.

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.

Complex regional pain syndrome type 1 and scurvy.

A 5 year old female developed features of complex regional pain syndrome (CRPS) i.e excessive pain to touch, decreased sweating and edema of left ankle 2 years after fracture of left tibia. Gum bleeding, petechiae and pseudoparalysis and suggestive radiograph characterized scurvy. Hyperesthesia improved and child walked with support following administration of vitamin C.

[Gaze-evoked suppression of the vestibular-ocular reflex in patients with posterior cervical sympathetic syndrome].

This vestibulometric (sinusoidal rotation) study included patients with posterior cervical sympathetic syndrome (n=40) and with vestibular neuronitis (n=20) as well as 20 healthy subjects of the control group. Vestibular dysfunction was induced by the method proposed by de Klein. The patients with posterior cervical sympathetic syndrome in the decompensation phase displayed abnormal gaze-evoked suppression of the vestibular-ocular reflex when their head movements lined up with sinusoidal rotation. This symptom is considered to be of primary value for the diagnosis of vestibular dysfunction in these patients.

Photophobia and neuropathic pain in Sudecks syndrome. / Fotofobia y dolor neuropático en el síndrome de Sudeck.

The case is presented of a 14 year-old patient diagnosed with Sudeck's syndrome secondary to uneventful foot trauma. The patient complained of decreased visual acuity along with photophobia and intense ocular pain not correlated with the exploratory findings. Sudeck's syndrome is an idiopathic neuropathic inflammatory disease characterised by disproportionate pain, unrelated to a previous traumatic event, which can evolve to severe and generalised pain. A new explanation has recently described this as "neuropathic eye pain" for those patients with severe eye pain that do not correlate with clinical signs. In the case presented here, the pain became widespread and led to photophobia and very intense ocular neuropathic pain. It is believed that this was the cause of the visual decrease presented by this patient. It is proposed that the Sudeck syndrome should become part of the differential diagnosis of neuropathic eye pain.

Nociceptive mechanisms involved in the acute and chronic phases of a complex regional pain syndrome type 1 model in mice.

Complex regional pain syndrome I (CRPS-I) is a chronic painful pathology still undertreated. CTK 01512-2 is a recombinant version of the spider peptide Phα1ß, and it functions as a voltage-gated calcium channel blocker and a transient receptor potential ankyrin 1 (TRPA1) antagonist with antinociceptive effect in different pain models. Here, we investigate the mechanisms involved in the acute and chronic nociceptive phases of a model of CPRS-I in mice and assess the antinociceptive effect of CTK 01512-2 using this model. Adult male and female mice C57BL/6 (20-30 g) were used to determine mechanical (von Frey test) or cold (acetone test) allodynia induction. Inflammatory parameters (serum and tibial nerve lactate levels, hind paw temperature and edema, or tissue cell infiltration) were evaluated after chronic post-ischemia pain (CPIP, a model of CPRS-I) induction. Anti-inflammatory and anti-neuropathic drugs or CTK 01512-2 were tested. First, we detected that CPIP-induced mechanical and cold allodynia in male and female mice in a similar way. In the acute phase (1 day after CPIP), an increase in inflammatory parameters were observed, as well as the anti-allodynic effect of anti-inflammatory compounds. In the chronic phase (17 days after CPIP), mice exhibited mechanical and cold allodynia, and anti-neuropathic drugs induced antinociception, while no inflammatory alterations were found. CTK 01512-2 reversed the CPIP allodynic effect in both nociceptive phases. Thus, this CPRS-I model can be used to understand the mechanisms involved in CPRS-I induced pain and inflammation. Besides, we observed that CTK 01512-2 has a valuable antinociceptive effect in this pain model.

Clinical Features of Pediatric Complex Regional Pain Syndrome: A 5-Year Retrospective Chart Review.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a painful condition of a limb characterized by a constellation of symptoms. Little is known about the clinical features of pediatric CRPS, with fewer than a dozen studies published to date. The aim of this study was to explore the clinical course of pediatric CRPS, with emphasis on clinical features and disease outcomes. A secondary aim was to discern differences in clinical features of pediatric CRPS with and without related movement disorders, and between children who had a favorable and unfavorable outcome. MATERIALS AND METHODS: We carried out a retrospective chart review of children with CRPS who presented to a pediatric Chronic Pain Clinic in Canada over a 5-year period (2012 to 2016). RESULTS: The study identified 59 children with CRPS (mean age: 12.7±2.5; 74.6% female; 72.9% lower extremity). In total, 87% (n=48) of children experienced complete resolution or significant improvement of CRPS, with a relapse rate of 15%. Overall, 25% (n=15) had a CRPS-related movement disorder. There were no differences in the clinical features of pediatric CRPS with or without related movement disorders. Children who experienced a favorable outcome had a significantly shorter symptom duration at the initial visit in comparison with children who experienced an unfavorable outcome. DISCUSSION: In this cohort, pediatric CRPS was most common in girls around the age of 12, usually in the lower extremity, and most experienced a favorable outcome. Further research is needed to better understand the prognosis and relapse rate of pediatric CRPS.