PMID: 

Physiother Theory Pract. 2020 Jan ;36(1):241-248. Epub 2018 Jun 6. PMID: 29873592

Abstract Title: 

Utilization of manual therapy to the lumbar spine in conjunction with traditional conservative care for individuals with bilateral lower extremity complex regional pain syndrome: A case series.

Abstract: 

: Conservative therapies for complex regional pain syndrome (CRPS) have traditionally focused on exercise and desensitization techniques targeted at the involved extremity. The primary purpose of this case series is to report on the potential benefit of utilizing manual therapy to the lumbar spine in conjunction with traditional conservative care when treating patients with lower extremity CRPS.: Two patients with the diagnosis of lower extremity CRPS were treated with manual therapy to the lumbar spine in conjunction with education, exercise, desensitization, and soft tissue techniques for the extremity.: Patient 1 received 13 sessions over 6 weeks resulting in a 34-point improvement in oswestry disability index (ODI) and 35-point improvement in lower extremity functional scale (LEFS). Patient 2 received 21 sessions over 12 weeks resulting in a 28-point improvement in ODI and a 41-point improvement in LEFS.: Both patients exhibited reductions in pain and clinically meaningful improvements in function. Manual therapies when applied to the lumbar spine in these patients as part of a comprehensive treatment plan resulted in improved spinal mobility, decreased pain, and reduction is distal referred symptoms. Although one cannot infer a cause and effect relationship from a case series, this report identifies meaningful clinical outcomes potentially associated with manual physical therapy to the lumbar spine for two patients with complex regional pain syndrome type 1.

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PMID: 

Med Hypotheses. 2010 Sep ;75(3):319-23. Epub 2010 Apr 7. PMID: 20378261

Abstract Title: 

Complex regional pain syndrome: a vitamin K dependent entity?

Abstract: 

Complex regional pain syndrome (CRPS) is the complication of some injuries, such as a fracture, which affects the distal end of the injured extremity characterized by pain, allodynia, hyperalgesia, edema, abnormal vasomotor and sudomotor activity, movement disorders, joint stiffness, regional osteoporosis, and dystrophic changes in soft tissue. Exact pathogenic mechanism of CRPS is still unclear. Suggested pathogenic mechanisms of CRPS are evaluated in four major groups consist of classic inflammation, hypoxic changes and chronic ischemia, neurogenic inflammation and sympathetic dysregulation. All of these suggested pathogenic mechanisms produced by inflammatory cytokines mediated by nuclear factor kappaB. Vitamin K is a family of structurally similar, fat-soluble, 2-methyl-1,4-naphthoquinones. Vitamin K exerts a powerful influence on bone formation, especially in osteoporosis. Fat in bone stores some vitamin K. Gamma-carboxylation of the glutamic acid in osteocalcin is vitamin K dependent. Osteocalcin plays a role in calcium uptake and bone mineralization. Osteocalcin, the most abundant non-collagenous protein in bone, is produced by osteoblasts during bone matrix formation. Because osteocalcin is not carboxylated in case of vitamin K deficiency at the distal site of fracture or injury, it cannot bind to hydroxyapatite causing osteoporosis. Fracture starts a local inflammatory process in the fracture site and adjacent tissues as seen in CRPS. Vitamin K was shown to suppress the inflammatory cytokines and NF-kappaB and prevent oxidative, hypoxic, ischemic injury (which have key role in both initiation and progression of CRPS) to oligodendrocytes and neurons. We hypothesized that vitamin K has a key role and modulatory effect in CRPS pathogenesis. Vitamin K deficiency at the distal site of fracture occurs because of diminished and slowed circulation, local immobilization after extremity fracture or injury and use of vitamin K store at the distal site of the injured extremity and in the circulation for fracture healing and bone remodelling. In case of vitamin K deficiency at the distal site of fracture, classic inflammation starts with fracture at the distal tissues could not be restricted and classic inflammation, hypoxic changes, chronic ischemia, neurogenic inflammation, sympathetic dysregulation, which are the pathogenic mechanisms of CRPS, and patchy osteoporosis which occur due to high level of under-carboxylated osteocalcin could not be prevented. Briefly vitamin K level decreases in the distal site of the injured extremity consequently resulting in patchy osteoporosis due to high level of under-carboxylated osteocalcin and unrestricted inflammation which are the cause for both initiation and progression of CRPS.

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PMID: 

Pain Pract. 2011 Mar-Apr;11(2):199-200. PMID: 21371256

Abstract Title: 

Is migraine a complex regional pain syndrome of the brain? Migraine prophylaxis with vitamin C?

Abstract: 

[n/a]

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PMID: 

Foot Ankle Surg. 2009 ;15(4):179-82. Epub 2009 Apr 5. PMID: 19840748

Abstract Title: 

Effect of vitamin C on prevention of complex regional pain syndrome type I in foot and ankle surgery.

Abstract: 

BACKGROUND: The public health cost impact of complex regional pain syndrome type I (CRPS I) is considerable in both emergency and scheduled orthopaedic surgery. We proposed to assess the effectiveness of vitamin C in prevention of CRPS I in foot and ankle surgery.METHODS: We carried out a"before-after"quasi-experimental study comparing two chronologically successive groups without (Group I: July 2002-June 2003) and with (Group II: July 2003-June 2004) preventive 1g daily vitamin C treatment. All patients having surgery on the foot or ankle were enrolled, with the exception of diabetic foot cases. Several factors were analysed: sex, age, type of pathology, history of CRPS I, psychological context, tourniquet time, and cast immobilisation time.RESULTS: 420 feet (392 patients) were included in the study: 185 in Group I, 235 in Group II. CRPS I occurred in 18 cases in Group I (9.6%) and 4 cases in Group II (1.7%) (p

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PMID: 

J Pain. 2018 10 ;19(10):1147-1156. Epub 2018 Apr 30. PMID: 29715519

Abstract Title: 

Oxidative Stress Contributes to Fracture/Cast-Induced Inflammation and Pain in a Rat Model of Complex Regional Pain Syndrome.

Abstract: 

: Clinical evidence suggests that vitamin C (Vit C) may protect against the development of complex regional pain syndrome (CRPS) after fracture or surgery. Tibia fracture followed by 4 weeks of cast immobilization (fracture/cast) in rats results in nociceptive, vascular, and bone changes resembling clinical CRPS. In this study, fracture/cast rats were treated with the oxidative stress inhibitors Vit C, N-acetyl cysteine, or 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl to examine their effects on CRPS-related nociceptive and vascular changes. Administration of these agents significantly reduced fracture/cast-induced cutaneous allodynia by 64 to 78%, muscle hyperalgesia by 34 to 40%, and hind limb unweighting by 48 to 89%. Treatments with Vit C and N-acetyl cysteine reduced the oxidative stress markers malondialdehyde in the skin, muscle, and sciatic nerve, and lactate in the gastrocnemius muscle of the fracture/cast limb. Furthermore, Vit C treatment inhibited the post-fracture upregulation of substance P and calcitonin gene-related peptide in the sciatic nerve and the increased expression of the pain-related inflammatory mediators, including interleukin (IL)-6, and nerve growth factor in the skin and IL-1β, and IL-6 in the muscle of the post-fracture/cast limb. These data suggest that oxidative stress may contribute to the nociceptive features of the rat CRPS model.PERSPECTIVE: Vit C reduced the CRPS-like signs, oxidative stress, and the upregulation of neuropeptide production and inflammatory mediators observed after tibia fracture and casting in rats. Limiting oxidative stress by use of Vit C or alternative strategies could reduce the risk of developing CRPS after surgery or other forms of trauma.

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PMID: 

Acta Anaesthesiol Scand. 2008 May ;52(5):688-94. PMID: 18419723

Abstract Title: 

Increased plasma glutamate, glycine, and arginine levels in complex regional pain syndrome type 1.

Abstract: 

BACKGROUND: Various inflammatory mediators have been identified as potential contributors to complex regional pain syndrome type 1 (CRPS1), but these mediators do not entirely explain certain manifestations of the syndrome, such as pain. The objective of this study was to investigate the role of amino acids in the pathogenesis of CRPS1.METHODS: We used HPLC to determine plasma concentrations of 16 amino acids, especially those related to the NMDA receptor (e.g., glutamate and glycine) and nitric oxide (NO) synthesis (e.g., arginine and citrulline) in patients with CRPS1 (n=64) and age- and sex-matched healthy controls (n=51). Patients rated pain intensity (visual analog scale) and the subjective experience of pain intensity (McGill Pain Questionnaire). Psychological dysfunction was assessed using the SCL-90.RESULTS: Relative to controls, in CRPS1 patients, plasma levels of glutamate, arginine, taurine, and glycine were increased, and plasma levels of glutamine and the ratio of citrulline to arginine were decreased. Remarkably, in CRPS1 patients there was a highly significant inverse correlation between glutamine and glutamate, although the sum of molar concentrations of glutamate and glutamine remains unchanged. Subjective measures of pain and indicators of psychoneuroticism and emotional instability did not correlate with amino acid levels.CONCLUSION: This study shows for the first time a pronounced increase in amino acid levels in this chronic pain syndrome. The marked differences in glutamate, glutamine, glycine, taurine and arginine levels between patients and controls suggest the involvement of both the NDMA receptor and the endothelium-dependent arginine-NO system in CRPS1.

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PMID: 

Pflugers Arch. 2018 12 ;470(12):1815-1827. Epub 2018 Aug 10. PMID: 30094478

Abstract Title: 

Electroacupuncture induces antihyperalgesic effect through endothelin-B receptor in the chronic phase of a mouse model of complex regional pain syndrome type I.

Abstract: 

Complex regional pain syndrome (CRPS) is a disorder that involves abnormal inflammation and nerve dysfunction frequently resistant to a broad range of treatments. Peripheral nerve stimulation with electroacupuncture (EA) has been widely used in different clinical conditions to control pain and inflammation; however, the use of EA in the treatment of CRPS is under investigation. In this study, we explore the effects of EA on hyperalgesia and edema induced in an animal model of chronic post-ischemia pain (CPIP model) and the possible involvement of endothelin receptor type B (ET) in this effect. Female Swiss mice were subjected to 3 h hind paw ischemia/reperfusion CPIP model. EA treatment produced time-dependent inhibition of mechanical and cold hyperalgesia, as well as edema in CPIP mice. Peripheral administration (i.pl.) of BQ-788 (10 nmol), an ETantagonist, prevented EA-induced antihyperalgesia while intrathecal administration prolonged EA's effect. Additionally, peripheral pre-treatment with sarafotoxin (SRTX S6c, 30 pmol, ETagonist) increased EA anti-hyperalgesic effect. Furthermore, the expression of peripheral ETreceptors was increased after EA treatments, as measured by western blot. These results may suggest that EA's analgesic effect is synergic with ETreceptor activation in the periphery, as well as central (spinal cord) ETreceptor blockade. These data support the use of EA as a nonpharmacological approach for the management of CRPS-I, in an adjuvant manner to ETreceptor targeting drugs.

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PMID: 

Pain Pract. 2019 03 ;19(3):289-294. Epub 2019 Jan 7. PMID: 30365222

Abstract Title: 

High-Frequency Spinal Cord Stimulation at 10 kHz for the Treatment of Complex Regional Pain Syndrome: A Case Series of Patients With or Without Previous Spinal Cord Stimulator Implantation.

Abstract: 

BACKGROUND: High-frequency spinal cord stimulation at 10 kHz (HF10-SCS) has been demonstrated to provide enhanced and durable pain relief in patients with chronic back and radiating leg pain. Patients with pain related to complex regional pain syndrome (CRPS) in the chronic stages are commonly challenging to treat and often receive traditional spinal cord stimulation (SCS). Very little information is currently available about the therapeutic outcomes following application of high-frequency stimulation in this cohort of patients.METHODS: The purpose of the retrospective case series was to report on the initial experience of HF10-SCS in 13 patients with CRPS, some of whom had been exposed to low-frequency SCS. A temporary trial of HF10-SCS was carried out for 1 week, and those achieving a minimum of 50% pain intensity reduction underwent implantation. Successful responders were those who achieved a 50% decrease in pain intensity on subsequent follow-up.RESULTS: Thirteen patients were trialed, 12 of whom went on to receive a permanent implant. Of the patients receiving permanent implants, the responder rate (50% pain relief) was 67% (95% confidence interval [CI] 0.34 to 0.90), with an average follow-up period of 12.1± 4.6 months. Of the 5 patients who had sympathetically independent pain, 3 were responders, and of the 7 patients who had sympathetically mediated pain, 5 were responders. There were no adverse events.CONCLUSION: This small case series suggests that HF10-SCS may be a viable option for patients with CRPS who have chronic intractable pain, including those who had suboptimal results from traditional SCS.

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PMID: 

Curr Pain Headache Rep. 2019 May 6 ;23(6):41. Epub 2019 May 6. PMID: 31062104

Abstract Title: 

Ozone Therapy for Complex Regional Pain Syndrome: Review and Case Report.

Abstract: 

PURPOSE OF REVIEW: The world faces a crisis in pain management. CRPS is a multifaceted painful disorder, which is difficult to treat and resolve. Ozone therapy has unique mechanisms of actions that may directly address the emerging discoveries of factors related to pathogenesis of the disorder and other pain conditions. These include oxygenation, immune modulation, anti-infective properties, and anti-inflammatory properties. This review is to present ozone therapy as a novel approach for pain treatment, including CRPS.RECENT FINDINGS: Ozone therapy has been found, in basic science studies, to ameliorate many of the mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection. Direct intravenous oxygen/ozone gas was administered nearly daily to an 11-year-old girl diagnosed with reflex sympathetic dystrophy and extremely frequent pseudoseizures. She rapidly improved. After 120 sessions, all symptoms had disappeared. Ozone's novel biochemical properties may make it a unique, safe, relatively inexpensive, and effective modality for the treatment of pain. In this particular case, it resolved the chronic condition when opiates were ineffective for even pain relief. Ozone therapy should be considered for institutional study despite its lack of financial reward (lack of patentability).PERSPECTIVE: This manuscript presents ozone therapy as a novel, safe, and inexpensive approach for RSD/CRPS, and an alternative to drugs. It is practiced worldwide and has abundant literature on its biochemical mechanisms, effectiveness for pain (and other conditions), and overall healing usefulness, yet little is known conventionally as it is not patentable.

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PMID: 

Front Pharmacol. 2019 ;10:453. Epub 2019 Apr 26. PMID: 31105572

Abstract Title: 

TRPV1 Channel Contributes to the Behavioral Hypersensitivity in a Rat Model of Complex Regional Pain Syndrome Type 1.

Abstract: 

Complex regional pain syndrome type 1 (CRPS-I) is a debilitating pain condition that significantly affects life quality of patients. It remains a clinically challenging condition and the mechanisms of CRPS-I have not been fully elucidated. Here, we investigated the involvement of TRPV1, a non-selective cation channel important for integrating various painful stimuli, in an animal model of CRPS-I. A rat model of chronic post-ischemia pain (CPIP) was established to mimic CRPS-I. TRPV1 expression was significantly increased in hind paw tissue and small to medium-sized dorsal root ganglion (DRG) neurons of CPIP rats. CPIP rats showed increased TRPV1 current density and capsaicin responding rate in small-sized nociceptive DRG neurons. Local pharmacological blockage of TRPV1 with the specific antagonist AMG9810, at a dosage that does not produce hyperthermia or affect thermal perception or locomotor activity, effectively attenuated thermal and mechanical hypersensitivity in bilateral hind paws of CPIP rats and reduced the hyperexcitability of DRG neurons induced by CPIP. CPIP rats showed bilateral spinal astrocyte and microglia activations, which were significantly attenuated by AMG9810 treatment. These findings identified an important role of TRPV1 in mediating thermal and mechanical hypersensitivity in a CRPS-I animal model and further suggest local pharmacological blocking TRPV1 may represent an effective approach to ameliorate CRPS-I.

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