Determinants of complex regional pain syndrome type I in patients with scaphoid waist fracture- a multicenter prospective observational study.

BACKGROUND: The aim of this prospective study was to assess the incidence of complex regional pain syndrome type I (CRPS I) in patients with scaphoid waist fracture and to explore associated factors. METHODS: This was a multicenter, prospective observational study. Demographic, imaging indicators and clinical data were collected before the conservative treatment of scaphoid waist fracture patients. The occurrence of CRPS I and pain condition were the main outcomes. To explore the factors associated with CRPS I, multivariate logistic regression model was used. RESULTS: A total of 493 scaphoid waist fracture participants undergoing conservative treatment were recruited for this study. The incidence of CRPS I was 20% (n = 87). The average time between injury and the onset of CRPS I was 6.7 ± 2.1 weeks. Multivariable logistic regression analysis revealed that female sex (odds ratio (OR): 1.669; 95% confidence interval (CI): 1.189-2.338), diabetes mellitus (OR: 3.206; 95% CI: 2.284-4.492), and severe pain condition before treatment (visual analog scale (VAS) score more than 4 cm) (OR: 27.966; 95% CI: 19.924-39.187) were independently associated with CRPS I. CONCLUSIONS: Patients suffering from scaphoid waist fracture may be at a higher risk of CRPS I, especially in women with diabetes mellitus who report severe pain before treatment. Early screening and regular follow up evaluation are recommended in these patients.

The superoxide scavenger tempol attenuates DNA oxidative injury and spontaneous pain-like behavior in chronic post-cast pain model rats.

The mechanism of severe pain occurring because of physical disuse, such as complex regional pain syndrome Type I, has not been elucidated so far. Therefore, to investigate this mechanism, we have developed a model called a chronic post-cast pain (CPCP) model. Oxidative stress-related factors generated in a fixed limb may be triggers for nociceptive signals due to physical disuse. On the basis of the results of our previous studies, we speculated that oxidative stress-related factors in immobilized hind limbs may also be triggers of nociceptive signals due to physical disuse. In this study, we aimed to clarify whether an oxidative stress-related factor is involved in the induction of nociceptive signals. The time course of oxidative damage in the soleus (slow-twitch fiber) and gastrocnemius (fast-twitch fiber) muscles was evaluated by immunostaining of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative damage in DNA). We also investigated the effects of tempol, a scavenger of superoxide, on oxidative damage in DNA, spontaneous pain-related behaviors (licking and/or biting and flinching), and the activation of spinal dorsal horn neurons (c-Fos). Systemic administration of tempol before cast removal attenuated oxidative damage to DNA in immobilized skeletal muscles, suppressed spontaneous pain-related behavior, and suppressed the activation of spinal dorsal horn neurons. We suggest that superoxide generated in immobilized skeletal muscles after cast removal is one of the peripheral factors that trigger nociceptive signals.

Effectiveness and Safety of Dorsal Root Ganglion Stimulation for the Treatment of Chronic Pain: A Pooled Analysis.

INTRODUCTION: Since it became available in the mid-2010s, dorsal root ganglion (DRG) stimulation has become part of the armamentarium to treat chronic pain. To date, one randomized controlled trial, and several studies of moderate sample size and various etiologies have been published on this topic. We conducted a pooled analysis to investigate the generalizability of individual studies and to identify differences in outcome between chronic pain etiologic subgroups and/or pain location. MATERIALS AND METHODS: One prospective, randomized comparative trial and six prospective, single-arm, observational studies were identified that met pre-defined acceptance criteria. Pain scores and patient-reported outcome (PRO) measures were weighted by study sample sizes and pooled. Safety data are reported in aggregate form. RESULTS: Our analysis included 217 patients with a permanent implant at 12-month follow-up. Analysis of pooled data showed an overall weighted mean pain score of 3.4, with 63% of patients reporting ≥50% pain relief. Effectiveness sub-analyses in CRPS-I, causalgia, and back pain resulted in a mean reduction in pain intensity of 4.9, 4.6, and 3.9 points, respectively. Our pooled analysis showed a pain score for primary affected region ranging from 1.7 (groin) to 3.0 (buttocks) and responder rates of 80% for foot and groin, 75% for leg, and 70% for back. A substantial improvement in all PROs was observed at 12 months. The most commonly reported procedural or device complications were pain at the IPG pocket site, lead fracture, lead migration, and infection. CONCLUSIONS: DRG stimulation is an effective and safe therapy for various etiologies of chronic pain.

Complex Regional Pain Syndrome Management: An Evaluation of the Risks and Benefits of Spinal Cord Stimulator Use in Pregnancy.

OBJECTIVE: We present a case of a young woman diagnosed with complex regional pain syndrome (CRPS) who underwent spinal cord stimulator (SCS) implantation. She had 2 successful pregnancies following implantation. DESIGN: We evaluated the electronic medical records of the patient following SCS implantation and while pregnant with her second and third children. A phone interview was conducted after her third pregnancy to discuss her experience with SCS use during and after pregnancy. SETTING: Physical medicine and rehabilitation pain management clinic and obstetrician clinic, affiliated with the Medical College of Wisconsin in Milwaukee, Wisconsin. SUBJECT: A 26-year-old woman with history of CRPS type I. RESULTS: This 26-year-old woman was diagnosed with CRPS type I after left knee surgery. All conservative treatments had failed prior to her undergoing SCS implantation after the birth of her first child. SCS implantation brought near complete resolution of her symptoms. When she became pregnant with her second child, she turned off her SCS. Her CRPS symptoms intensified, but she had a normal pregnancy. She turned the SCS back on postpartum and elected to continue its use throughout her third pregnancy. She had a normal pregnancy, and her CRPS symptoms were well controlled. The patient and her children are currently healthy. Her SCS remains functional and effective. CONCLUSION: Both an SCS and many medications used for pain management in CRPS could cause harm to both mother and fetus in pregnancy. Further research must be done to determine the safety and efficacy of SCS use in pregnancy.

Ultrasound-Guided Intra-articular Injection of the Radio-ulnar and Radio-humeral Joints and Ultrasound-Guided Dry Needling of the Affected Limb Muscles to Relieve Fixed Pronation Deformity and Myofascial Issues around the Shoulder, in a Case of Complex Regional Pain Syndrome Type 1.

BACKGROUND: Complex regional pain syndrome (CRPS) occurs due to different pathophysiological mechanisms. Presently there is no description of definitive treatment that can resolve the especially recalcitrant motor issues of disability in CRPS type 1 (CRPS-1). CASE REPORT: We have herein described the successful management of motor disability with a multimodal approach in a patient with CRPS-1 that occurred as a result of a fracture sustained in the lower end of the radius. Sensory/sudomotor/vasomotor symptoms were relieved completely by medications and stellate ganglion block in 2 weeks. Ultrasound-guided dry needling secured near-complete improvement of shoulder and hand movements in 45 days. Ultrasound guided intra-articular (radio-ulnar and radio-humeral joint) injections with steroid reduced residual pain and improved forearm movements by 50% initially. The patient continued to receive regular sessions of dry needling, physiotherapy, and cognitive behavioral therapy. By the end of 1 year, the functions of the limb improved remarkably, as did the functional outcome scores. CONCLUSION: In this patient with CRPS-1, intra-articular injections with steroid reduced nociception in the affected local structures and sensitization in the nervous system; dry needling resolved the myofascial issues; sustained physiotherapy maintained the motor recovery; and behavioral therapy techniques addressed the cognitive and life stress issues. It was concluded that the presenting symptoms in this case were a consequence of interactions between humoral, nervous, and myofascial systems.

Management of patients with complex regional pain syndrome type I.

Complex regional pain syndrome type I (CRPS-I) includes different conditions characterized by regional pain and sensory, motor, sudomotor, vasomotor, and/or trophic findings, affecting a peripheral limb usually after a noxious event, such as a trauma or surgery. The pathophysiology is still poorly understood. Limited data are available on the incidence of CRPS-I, and the disease is underestimated and under-diagnosed. The disease shows a female preponderance approximately 3:1 with a peak age of incidence around the 5th and 6th decade. The available diagnostic criteria for CRPS-I rely on clinical criteria that are unfortunately focused on the signs and symptoms of the chronic and late disease, while little emphasis is given to the typical imaging (X-rays, bone scintigraphy, MRI) findings of the early phase. Over the last decades, several therapies have been proposed but the few studies available are often too small to be conclusive and rarely evolved to randomized controlled trials (RCTs). On the basis of the results of a few RCTs, only short courses of high bisphosphonate doses appear to provide substantial benefits. The best results are seen in patients in the early phase of the disease, often with the persistent remission or complete healing of the conditions. Since the only accredited mechanism of action of bisphosphonates is the suppression of osteoclastic bone resorption, it is likely the initial dramatic bone loss plays a role in the maintenance and evolution of CRPS-I. Short courses of high doses of bisphosphonates should be considered the treatment of choice for patients with CRPS-I.

Musculoskeletal Ultrasonography to Distinguish Muscle Changes in Complex Regional Pain Syndrome Type 1 from Those of Neuropathic Pain: An Observational Study.

Musculoskeletal ultrasonography (MSK USG) can identify myofascial structural lesions. We describe in this retrospective report the observational findings of USG data of muscles from limbs affected with neuropathic pain in 7 patients and compare them with muscles affected with complex regional pain syndrome type 1 (CRPS-1) in 7 patients. We highlight findings that distinguish between the 2 conditions. Musculoskeletal ultrasonography of muscles in CRPS was characterized by a variable or/and global intramuscular structural disruption with loss of muscle bulk. Adjacent muscles coalesced with one another to present an uniform hyperechogenic mass of tissue. Muscle edema was found in some patients. In comparison, MSK USG in muscles affected by neuropathic pain exhibited structural normalcy, but also showed considerable reduction in muscle bulk. Musculoskeletal ultrasonography shows promise as a diagnostic modality to distinguish between these 2 conditions which presently have only clinical diagnostic criteria to aid diagnosis.

Successful treatment of intractable complex regional pain syndrome type I of the knee with dorsal root ganglion stimulation: a case report.

OBJECTIVES: To report on the efficacy of dorsal root ganglion stimulation in a patient with complex regional pain syndrome (CRPS) type I of the knee. MATERIALS AND METHODS: A 48-year-old woman with CRPS type I of the right knee, diagnosed according to the Budapest criteria set, received DRG stimulation for intractable CRPS type I of the knee. RESULTS: After a successful trial period with three DRG stimulation leads on spinal levels L2, L3, and L4 (covering 90% of the painful area of her knee), a definitive pulse generator was implanted. Three months after implantation, the entire painful area was covered, and the patient reported a numeric rating scale score of 1-2. CONCLUSION: Placement of three DRG stimulation leads at levels L2, L3, and L4 in a patient with intractable CRPS type I of the knee resulted in major pain relief. We recommend further investigation of the effect of DRG stimulation on pain due to CRPS of the knee.

Teriparatide and clodronate combination as a potential treatment for complex regional pain syndrome type I in delayed consolidation after foot surgery: a case report and review of the literature.

BACKGROUND: Complex regional pain syndrome type I is a pathological condition characterized by an exaggerated response of tissues to low or moderate pain stimuli. The exact pathogenesis and optimal medical treatment for complex regional pain syndrome type I are still not fully understood, although bisphosphonates have shown positive effects in reducing pain. Foot surgery can be complicated by the development of complex regional pain syndrome type I, leading to functional decline and difficulties in weight-bearing. CASE PRESENTATION: The authors present a clinical case involving complex regional pain syndrome type I that developed after surgical foot arthrodesis. The patient, a 42-year-old Caucasian male, did not respond to clodronate treatment but experienced successful outcomes upon the addition of teriparatide, which effectively stimulated the healing of arthrodesis. CONCLUSION: Teriparatide cannot be considered the primary treatment for complex regional pain syndrome due to insufficient solid clinical data. However, when complex regional pain syndrome is associated with or caused by delayed union, teriparatide can be used to address the underlying cause of complex regional pain syndrome.

Spinal cord stimulation for complex regional pain syndrome type I: a prospective cohort study with long-term follow-up.

OBJECTIVES: Spinal cord stimulation (SCS) is an effective treatment for intractable complex regional pain syndrome type I pain. Long-term data are scarce on effectiveness, degree of pain relief, predictors, and complications. MATERIALS AND METHODS: From 1997 to 2008, 84 consecutive patients who received an implanted SCS system after positive test stimulation were included in the prospective study. Treatment effectiveness was assessed annually as measured by mean visual analog scale pain scores and with the Patients Global Impression of Change scale. Treatment success was defined as at least 30% mean pain relief at end point and treatment failure as explantation of the system. A Cox regression determined if baseline factors were associated with both these outcomes. RESULTS: During 11 years, 41% (95% CI: 27-55) of the patients experience at least 30% pain relief at assessment end point. During 12 years of follow-up 63% (95%CI: 41-85) of the implanted patients still use their SCS device at measured end point. Pain relief of at least 50% one week following test stimulation is associated with a higher probability of long-term treatment success. In 51 patients, 122 reinterventions were performed over 12 years; 13 were due to complications, 44 to battery changes, and 65 reinterventions were equipment related. CONCLUSION: SCS provides an effective long-term pain treatment for 63% (95%CI: 41-85) of implanted patients. Forty-one percent (95%CI: 27-55) of SCS treated patients have at least 30% pain reduction at measurement end point. The number of reinterventions after implantation due to equipment-related problems, battery changes, and complications is 122 over 12 years of follow-up. Sixty-one percent (N = 51) of the patients had at least one reintervention. Mean pain relief of at least 50% (visual analog scale) one week after the test stimulation is associated with long-term treatment success.

Complex Regional Pain Syndrome Type I: Evidence for the CB1 and CB2 Receptors Immunocontent and Beneficial Effect of Local Administration of Cannabidiol in Mice.

Introduction: Complex regional pain syndrome type I (CRPS-I) is a debilitating neuropathic painful condition associated with allodynia, hyperalgesia, sudomotor and/or vasomotor dysfunctions, turning investigation of its pathophysiology and new therapeutic strategies into an essential topic. We aim to investigate the impact of ischemia/reperfusion injury on the immunocontent of CB1 and CB2 cannabinoid receptor isoforms in the paws of mice submitted to a chronic postischemia pain (CPIP) model and the effects of local administration of cannabidiol (CBD) on mechanical hyperalgesia. Methods: Female Swiss mice, 30-35 g, were submitted to the CPIP model on the right hind paw. Skin and muscle samples were removed at different periods for western blot analysis. Results: No changes in the immunocontent of CB1 and CB2 receptors in paw muscle tissues after ischemia-reperfusion were observed. CBD promoted an antihyperalgesic effect in both phases. AM281 reversed the effect of CBD, whereas ruthenium red abolished the late phase. Conclusion: Our results point to the possible beneficial effects of local administration of CBD in modulating CRPS-I in humans. As possible targets for CBD antihyperalgesia in this model, the contribution of cannabinoid receptor CB1, in addition to TRPM8 is suggested.

Diagnosis of complex regional pain syndrome type 1 in patients with corticobasal degeneration: a case report.

We report a rare case of a patient with corticobasal degeneration (CBD) who was also diagnosed with complex regional pain syndrome type I (CRPS I), which has similar clinical characteristics. A 76-year-old man who had been diagnosed with CBD several years prior presented with asymmetric severe pain, postural instability, limb rigidity, limb dystonia, tremor, ideomotor apraxia, and bradykinesia especially on his left upper extremity on admission at our rehabilitation center. Additional physical examination showed darkened skin color change, edema, reduced skin elasticity, cold skin temperature, wet skin, and limited range of motion (ROM) of the left side compared to the right side. A three-phase bone scan was done resulting CRPS I. Therefore, we initiated treatment for CRPS I, including steroid pulse therapies and non-steroidal anti-inflammatory drugs (NSAID); subsequently, his left extremity pain reduced from a visual analogue scale (VAS) score of 8-9 to 3 and his functional level also improved. To the best of our knowledge, this is the first case report of a CBD patient being also diagnosed with CRPS I. Due to the similar clinical characteristics that two diseases share, we would like to inform the physicians the importance of differentiating the CRPS I from CBD for the quick proper management.

A Randomized Comparison between 4, 6 and 8 mL of Local Anesthetic for Ultrasound-Guided Stellate Ganglion Block.

BACKGROUND: Because it affords greater accuracy than landmark-based techniques, ultrasound guidance may reduce the volume of local anesthetic required for sympathetic blockade of the upper extremity. We hypothesized that 4 mL would provide a similar clinical effect when compared to larger volumes. METHODS: One hundred and two patients with chronic neuropathic pain of the upper extremity or face were randomly assigned to receive an ultrasound-guided (USG) stellate ganglion block (SGB) with either 4 mL (group A), 6 mL (group B) or 8 mL (group C) mL of 1.0% lidocaine. Skin temperatures of the face, hand, and axillary fold were measured bilaterally at baseline, 10, 20, and 30 min after the block. Our primary outcome was the relative increase in hand temperature on the blocked side at 30 min and our non-inferiority margin was -0.6 °C. Secondary outcomes included success rate (as defined by a relative temperature increase of ≥1.5 °C), pain relief, degree of ptosis and side-effects. RESULTS: The 95% confidence intervals for the difference of the means exceeded our non-inferiority margin (A versus B: -0.76 to 0.24; A versus C: -0.89 to 0.11) for temperature changes in the hand; however, success rates were similar (44, 45 and 55% for A, B and C respectively, p = 0.651). No intergroup differences were found in temperature-related outcomes for the other measurement sites (face, axilla). The incidence of minor side-effects was significantly higher in group C and no block-related complications were noted. CONCLUSIONS: We were unable to establish the non-inferiority of a 4 mL volume for sympathetic blockade of the hand. The clinical significance of these findings is unclear as success rates were similar between the different groups. In contrast, the 6- and 8 mL volumes were not associated with greater temperature changes in the face and axilla.

Does Temperature Increase by Sympathetic Neurolysis Improve Pain in Complex Regional Pain Syndrome? A Retrospective Cohort Study.

BACKGROUND: Lumbar sympathetic neurolysis (LSN) is a treatment option for complex regional pain syndrome (CRPS). We examined whether LSN-related temperature changes are associated with clinical outcome and investigated relationships between the outcome of LSN and clinical variables in patients with CRPS-I. METHODS: We included 95 patients with CRPS-I affecting a single lower extremity, by the Budapest criteria, and who underwent LSN after successful lumbar sympathetic blocks, in this retrospective study. Fluoroscopy-guided LSN was conducted with 1.5 mL of 99% alcohol at L2 and L3 vertebral levels. Positive outcome was defined as a reduction of ≥50% on a numeric rating scale pain score at 6 months after LSN. The relationship between successful outcome and clinical variables was analyzed. RESULTS: Positive LSN outcome occurred in 49.5% of patients, and it was suggested that Sympathetically maintained pain may accompany CRPS-I in 28% of patients. The overall temperature in the affected limb was increased after LSN, without contralateral limb temperature changes, but did not differ significantly between the positive and negative outcome groups (P = 0.590). Temperature after LSN in warm-type CRPS was reduced in the affected limb, without contralateral limb temperature changes. The absolute temperature change was significantly greater in cold-type than in warm-type CRPS (P = 0.026). In multivariate analysis, a short duration of pain and concurrent cold intolerance were significant factors predicting a positive outcome after LSN. CONCLUSIONS: LSN may be effective in some patients with CRPS, irrespective of temperature changes and temperature asymmetry pattern. A short duration of pain and concurrent cold intolerance significantly predict successful LSN.

Recovery from acute pediatric complex regional pain syndrome type I after ankle sprain by early pharmacological and physical therapies in primary care: a case report.

BACKGROUND: Complex regional pain syndrome type I (CRPS I) in children is a serious condition disrupting the family and school life of patients with the condition after it fully develops. It has been emphasized that early diagnosis is closely associated with earlier reduction of pain leading to preferable outcomes. OBJECTIVES: To report a case of acute CRPS I in a boy who was found to develop this condition by a routine visual analog scale (VAS) pain monitoring and who recovered from CRPS I at an early phase by prompt pharmacological, physical, and educational therapies. STUDY DESIGN: Case report. CASE REPORT: A 12-year-old boy sprained his left ankle while playing soccer and was referred to our clinic 4 days after the injury. At the first visit, he could walk, reporting motion pain with a VAS scale of 80 mm. On day 5, pain intensity increased to 100 mm, and a diagnosis of acute CRPS I was made. On day 7, he could not move the injured ankle; therefore celecoxib and pregabalin were administered, and physical and educational therapies started. On day 35, pain intensity was 0 mm and he could walk and run normally. CONCLUSION: Routine monitoring of VAS for every patient in pain is useful to discover an abnormal transition of VAS, enabling the early diagnosis of CRPS I. Inflammation and peripheral or central sensitization are postulated for early development of CRPS I. The present case suggested a combination of physical therapy and pharmacological intervention with celecoxib and pregabalin reduced peripheral and central sensitization.

Complex regional pain syndrome type I in children: What is new?

Complex regional pain syndrome type I (CRPS-I), although first described by the French surgeon Ambroise Paré as far back as the 16th century, nevertheless remains shrouded in mystery. The most common symptoms are pain in an entire hand or foot, allodynia, functional impairment induced by the pain, local oedema and skin color changes and transient sweating abnormalities. Most cases occur after a minor injury (i.e., a sprain or fracture), although there may be no identifiable triggering event, particularly in children. Primarily cold CRPS-I is by far the most common variant in children. Development of the Budapest criteria has benefited the diagnosis. These criteria are clinical and no specific diagnostic investigation is available. In vitro and in vivo studies have established that several pathogenic mechanisms can be involved concomitantly. However, there is no satisfactory explanation to the full clinical spectrum. Blood tests and imaging studies are useful for ruling out other diagnoses then monitoring the course of the condition, which may involve the development of demineralisation or osteopenia. High-resolution peripheral quantitative computed tomography may be helpful, as it provides quantitative assessments of the cortical and trabecular bone. CRPS-I has several specific characteristics in children compared to adults and whether the condition is the same entity in these two age groups is a legitimate question. The optimal management involves an early diagnosis followed by a multidisciplinary management programme of functional rehabilitation therapy and cognitive behavioral therapy. Analgesics are useful only during the phase of acute pain and to facilitate physical therapy. Studies in adults showed that bisphosphonates were effective within the first 12 months after symptom onset and calcitonin in longer-lasting cases. No high-quality clinical research studies into the aetiopathogenesis and treatment of CRPS-I in children and adolescents are available to date.

Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis.

BACKGROUND: Complex regional pain syndrome type I (CRPS-I), previously known as reflex sympathetic dystrophy, is common after conservatively or surgically treated wrist fractures. Several studies support the efficacy of vitamin C in preventing CRPS-I, although the data are somewhat conflicting. The primary objective of this systematic literature review and meta-analysis was to assess the efficacy of vitamin C therapy in preventing CRPS-I after a wrist fracture. METHODS: Randomised, placebo-controlled trials of vitamin C to prevent CRPS-I after wrist fractures were sought in the three main databases: PubMed (1980 to December 2015), CENTRAL (Central 2015, number 12), and Embase (1980 to December 2015). Two authors worked independently to select articles. Data from selected articles were collected independently. RESULTS: Three randomised placebo-controlled trials in a total of 875 patients were included. Treatment was non-operative in 758/890 (85.1%) fractures and operative in 132 (14.9%) fractures. Vitamin C supplementation was started on the day of the injury and continued for 50 days. In the group given 500mg of vitamin C daily, the risk ratio for CRPS-I was 0.54 (95%CI, 0.33-0.91; P=0.02). Thus, the risk of developing CRPS-I was significantly decreased by prophylactic treatment with 500mg of vitamin C per day. The heterogeneity rate was 65% (non-significant). CONCLUSION: Daily supplementation with 500mg of vitamin C per day for 50 days decreases the 1-year risk of CRPS-I after wrist fracture. LEVEL OF EVIDENCE: II, systematic review of level I and II studies.

Dexmedetomidine alleviates rat post-ischemia induced allodynia through GRK2 upregulation in superior cervical ganglia.

A transient decrease in G protein-coupled receptor kinase 2 (GRK2) in nociceptors can produce long-lasting neuroplastic changes in nociceptor function, eventually enhancing and prolonging inflammatory hyperalgesia. Here, we investigated the effects of selective α2-adrenoceptor agonist dexmedetomidine (DMED) on GRK2 expression in superior cervical ganglion (SCG) in a rat model of complex regional pain syndrome type I (CRPS-I). The ipsilateral 50% paw withdrawal thresholds (PWTs) to mechanical stimuli decreased significantly starting from 24 h after ischemia-reperfusion (I/R) injury, and lasted for over 3 weeks; the ipsilateral cold allodynia scores, GRK2 protein and mRNA levels in SCGs all increased significantly. No significant differences were found in the contralateral side except GRK2 mRNA reduced significantly after 48 h I/R injury, but still higher than those in the ipsilateral side. Following daily injection of 10 µg/kg of DMED for a maximum of 7 days, the ipsilateral PWTs on days 1, 2, 7, 14, and 21 after DMED administration were significantly higher than those in control group; the GRK2 protein and mRNA expressions in the ipsilateral SCGs were also significantly upregulated; the ipsilateral cold allodynia scores were significantly reduced. No significant differences were found in the contralateral 50%PWTs, cold allodynia scores, and GRK2 protein level except GRK2 mRNA levels increased significantly on days 1 to 7 after DMED administration. Therefore, a transient decrease of GRK2 expression in SCG neurons might be involved in the development and maintenance of allodynia in CRPS-I and DMED might alleviate this allodynia through GRK2 upregulation in SCG neurons.

Paroxetine alleviates rat limb post-ischemia induced allodynia through GRK2 upregulation in superior cervical ganglia.

Long-lasting neuroplastic changes induced by transient decrease in G protein-coupled receptor kinase 2 (GRK2) in nociceptors enhances and prolongs inflammatory hyperalgesia. Here, we investigated the effects of paroxetine (a selective serotonin reuptake inhibitor and GRK2 inhibitor) on GRK2 expression in superior cervical ganglion (SCG) in a rat model of complex regional pain syndrome type I (CRPS-I). After ischemia-reperfusion (I/R) injury, the ipsilateral 50% paw withdrawal thresholds (PWTs) to mechanical stimuli and the expression levels of GRK2 protein and mRNA in the ipsilateral SCGs all decreased significantly; the ipsilateral cold allodynia scores increased significantly. No significant differences were found in the contralateral side except GRK2 mRNA reduced significantly at day 2-day 9 after I/R injury, but still higher than those in ipsilateral SCGs. After paroxetine administration, the ipsilateral 50% PWTs at day 2, 7, 14, and 21 were significantly higher than those in control group; The GRK2 protein and mRNA levels in ipsilateral SCGs were also significantly up-regulated after day1; The ipsilateral cold allodynia scores were significantly reduced after day7. No significant differences were found in the contralateral 50% PWTs, cold allodynia scores, and GRK2 protein level except GRK2 mRNA levels increased significantly at day1-day7 after paroxetine administration. Therefore, a transient decrease of GRK2 expression in SCG neurons might be involved in the development and maintenance of allodynia in CRPS-I and paroxetine might alleviate this allodynia through GRK2 protein upregulation in SCGs.