The Possible Pathophysiological Mechanism behind Chronic Regional Pain Syndrome - Coursework Example

THE POSSIBLE PATHOPHYSIOLOGICAL MECHANISM BEHIND CHRONIC REGIONAL PAIN SYNDROME The Chronic Regional Pain Syndrome, also known as Clausalgia, CRPS or Reflex sympathetic dystrophy, is a complex and chronic pain condition. The main symptom representing this disease is an intense pain, out of proportion to the level of injury, which goes on worsening rather than getting better with time. It is an uncommon condition, affecting mostly one arm or leg. Rarely, other parts of the body are affected. The associated symptoms include swelling, discoloration, altered temperature, abnormal sweating and hypersensitivity in the affected area. Women are more commonly affected by this disease compared to men. Although it is most common in people between the ages of 40 and 60, it can occur at any age. Treatment for the chronic regional pain syndrome is most effective when started early in the course of the syndrome. Formerly, CRPS was called as the Reflex Sympathetic Dystrophy. It is affecting as many as 1.5 million Americans. The name was changed because it is not entirely clear that the over activity of the sympathetic nervous system is involved. The condition was first called as Clausalgia in 1864, during the Civil War. The soldiers noted burning pain, progressive skin changes, and decreased function in an affected limb. The prognosis of this disease varies from patient to patient. The International Association for the Study of Pain has divided CRPS into two types based on the presence of nerve lesion following the injury. Type I, also known as Reflex Sympathetic Dystrophy (RSD), Sudecks atrophy, Reflex Neurovascular Dystrophy (RND) or Algoneurodystrophy, does not have demonstrable nerve lesions. Type II, also known as Causalgia, has evidence of obvious nerve damage. STAGES: CRPS has three stages. Stage 1, the acute stage usually lasts for about three months and is usually characterized by servere burning, redness, aching pain, swelling, increased nail and hair growth and increased temperature. Stage 2, which lasts approximately for about three to six months, is called the ‘dystrophic stage’. It is characterized by the diffused pain, hair loss, spotty osteoporosis, increased joint thickness, muscle wasting, brittle and grooved nails, skin changes, pale and cold skin and reduction in range of motion. Stage 3, called the ‘atrophic stage’, is characterized by the pain spreading to entire limb or the body. There is extreme weakness of the joints, atrophy of muscles and the bone loss. Edema photo in CRPS (3) Venipuncture CRPS II, five months after a blood test, resulted in neuroinflammatory bulbous lesions. (3) The lesion became ulcerated (3) The lesion healed after treatment with I.V. mannitol and I.V. immunoglobulin treatment(3) ETIOLOGY: CRPS may develop after a limb trauma like in accidents, fractures, surgeries or even mild injuries such as IV insertions. Interestingly, a heart attack can also trigger CRPS in hand. Injury of the hip can cause foot pain and injury of the shoulder can cause hand pain. RISK FACTORS: (4) 1. Head injury 2. Stroke 3. Polio 4. Amyotropic lateral sclerosis (ALS) 5. Myocardial infarction 6. Polymyalgia rheumatica 7. Operative procedures e.g Carpal tunnel release 8. Brachial plexus pathology 9. Cast/splint immobilization 10. Minor injury of an extremity 11. Prolonged bedrest POSTULATED MECHANISMS: The exact mechansim for complex regional pain syndrome is still not clearly understood. It may develop after limb trauma, and is characterized by pain, sensory-motor and autonomic symptoms. Major mechanisms for CRPS, which might be present subsequently, or in parallel during the course of CRPS, are: 1. Trauma related cytokine release. 2. Exaggerated neurological inflammation 3. Sympathetically maintained pain 4. Cortical reorganisation in response to chronic pain, also known as ‘neuroplasticity’. 5. Pathological sympath-afferent coupling. 6. Accumulating evidence shows that genetic factor may predispose for CRPS. The recognition of these mechanisms in individual CRPS patient is the pre-requisit for a mechanism-oriented treatment. This medical exhibit accurately depicts the complex chain of events involved with reflex sympathetic dystrophy (RSD) of the hand and wrist. The pain pathway of RSD, also known as Complex Regional Pain Syndrome, or CRPS, is shown originating in the hand, following a course to the brain, triggering a sympathetic inflammatory response (blood vessel spasms), resulting in burning, pain and swelling at the injury site.(5) Post-traumatic Reflex Sympathetic Dystrophy (RSD) of the Upper Extremity and Hand (6) 1. TRAUMA RELATED CYTOKINE RELEASE: According to a study carried out by the Department of Neurology, Drexel University College of Medicine, USA, CRPS Type I and Type II are charecterized by various combinations of sensory, autonomic and motor abnormalities. In animal studies, conditions resulting in the exaggerated pain states demonstrate elevated pro-inflammatory cytokines. In addition, the pro-inflammatory cytokines have been shown to induce or increase neuropathic and inflammatory pain. In this research, utilizing high sensitivity enzyme linked immunosorbant assay (ELISA), the levels of pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin 6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α) in the cerebrospinal fluid of patients affected with CRPS were compared to the CSF levels found in other patients with and without painful conditions. The results from this study demonstrated significant increases in IL-1β and IL-6, but not TNF-α in the CSF of individuals afflicted with CRPS as compared to controls. CSF cytokine conditions in controls with painful conditions did not differ from levels in controls without pain. Furthermore, these increases showed no relation with the patient’s gender or weight. These results are consistent with the studies that suggest that the pathogenesis of CRPS is due in part to the central neuroimmune activation. (1). Another study carried out by Ucevler N, Eberle T, Rolke R, Birkelein F and Sommer C at Department of Neurology, University of Wurzberg, Germany is described below: The main purpose was to investigate, whether patients with CRPS have altered systemic pro- and anti-inflammatory cytokine profiles compared to controls on mRNA and protein level. The blood cytokine mRNA and protein levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF), interleukin-2 (IL-2) and IL-8 and the anti inflammatory cytokines IL-4, IL-10, and transforming growth factor-beta1 (TGF beta 1) in 40 prospectively recruited patients with CRPS I, two patients with CRPS II, and 34 controls were studied. Quantitative real-time PCR and enzyme linked immunosorbent assay were used. Additionally, the patients underwent quantitative sensory testing and were assessed with the McGill pain questionnaire and the Hospital anxiety and depression scale. Patients with CRPS had higher blood TNF and IL-2 mRNA levels (p=0.005; p=0.04) and lower IL-8 mRNA levels (p Read More