George Groeneweg

Effect of tadalafil on blood flow, pain, and function in chronic cold Complex Regional Pain Syndrome: A randomized controlled trial

BackgroundThis double-blind, randomized, controlled trial investigated the effect of the phosphodiesterase-5 inhibitor tadalafil on the microcirculation in patients with cold Complex Regional Pain Syndrome (CRPS) in one lower extremity.MethodsTwenty-four patients received 20 mg tadalafil or placebo daily for 12 weeks. The patients also participated in a physical therapy program. The primary outcome measure was temperature difference between the CRPS side and the contralateral side, determined by measuring the skin temperature with videothermography. Secondary outcomes were: pain measured on a Visual Analogue Scale, muscle force measured with a MicroFet 2 dynamometer, and level of activity measured with an Activity Monitor (AM) and walking tests.ResultsAt the end of the study period, the temperature asymmetry was not significantly reduced in the tadalafil group compared with the placebo group, but there was a significant and clinically relevant reduction of pain in the tadalafil group. Muscle force improved in both treatment groups and the AM revealed small, non-significant improvements in time spent standing, walking, and the number of short walking periods.ConclusionTadalafil may be a promising new treatment for patients that have chronic cold CRPS due to endothelial dysfunction, and deserves further investigation.Trial RegistrationThe registration number in the Dutch Trial Register is ISRCTN60226869.

Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management

BackgroundDuring the chronic stage of Complex Regional Pain Syndrome (CRPS), impaired microcirculation is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Several mechanisms may be responsible for the ischemia and pain in chronic cold CPRS.DiscussionThe diminished blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating catecholamines, or endothelial dysfunction. The pain may be of neuropathic, inflammatory, nociceptive, or functional nature, or of mixed origin.SummaryThe origin of the pain should be the basis of the symptomatic therapy. Since the difference in temperature between both hands fluctuates over time in cold CRPS, when in doubt, the clinician should prioritize the patients report of a persistent cold extremity over clinical tests that show no difference. Future research should focus on developing easily applied methods for clinical use to differentiate between central and peripheral blood flow regulation disorders in individual patients.

Effect of immunomodulating medications in complex regional pain syndrome: a systematic review.

Background:Different mechanisms are involved in a complex network of interactions resulting in the painful and impairing disorder, complex regional pain syndrome (CRPS). There is convincing evidence that inflammation plays a pivotal role in the pathophysiology of CRPS. Immunomodulating medication reduces the manifestation of inflammation by acting on the mediators of inflammation. Therefore, as inflammation is involved in the pathophysiology of CRPS, immunomodulating medication in CRPS patients may prove beneficial. Objectives:To describe the current empirical evidence for the efficacy of administering the most commonly used immunomodulating medication (ie, glucocorticoids, tumor necrosis factor-&agr; antagonists, thalidomide, bisphosphonates, and immunoglobulins) in CRPS patients. Methods:PubMed was searched for original articles that investigated CRPS and the use of one of the abovementioned immunomodulating agents. Results:The search yielded 39 relevant articles: from these, information on study design, sample size, duration of disease, type and route of medication, primary outcome measures, and results was examined. Discussion:Theoretically, the use of immunomodulating medication could counteract the ongoing inflammation and might be an important step in improving a disabled hand or foot, leading to further recovery. However, more high-quality intervention studies are needed.

Vasodilative Effect of Isosorbide Dinitrate Ointment in Complex Regional Pain Syndrome Type 1

Background In complex regional pain syndrome type 1 (CRPS1) vascular changes occur from the initial, inflammatory event onto the trophic signs during chronicity of the disease, resulting in blood flow disturbances and marked temperature changes. Pharmacotherapeutic treatment is generally inadequate. Aim To determine whether local application of the nitric oxide donor isosorbide dinitrate (ISDN) could cause vasodilation and thereby improve tissue blood distribution in the affected extremity. Methods In a pilot study, 5 female patients with CRPS1 in one hand were treated with ISDN ointment 4 times daily during 10 weeks. As a primary objective videothermography was used to monitor changes in blood distribution in both the involved and contralateral extremities. Results Patients treated with ISDN showed an increase of 4°C to 6°C in mean skin temperature of the cold CRPS1 hands, reaching values similar to that of the contralateral extremities within 2 to 4 weeks time, suggesting normalization of blood distribution. This was confirmed by an improvement in skin color. In 3 patients the Visual Analog Scale pain declined, whereas in the other 2 patients the Visual Analog Scale pain was unchanged over time. Conclusions In this pilot study, topical application of ISDN seems to be beneficial to improve symptoms for patients with cold type CRPS1, but further study is needed.

Report of a Preliminary Discontinued Double‐Blind, Randomized, Placebo‐Controlled Trial of the Anti‐TNF‐α Chimeric Monoclonal Antibody Infliximab in Complex Regional Pain Syndrome

Inflammation appears to play a role in CRPS as, for example, cytokines (like TNF‐α) are involved in the affected limb. The ongoing inflammation is probably responsible for the central sensitization that sometimes occurs in CRPS. Thus, early start of a TNF‐α antagonist may counteract inflammation, thereby preventing rest damage and leading to recovery of the disease.

Mast cells: a new target in the treatment of complex regional pain syndrome?

There is convincing evidence that inflammation plays a pivotal role in the pathophysiology of complex regional pain syndrome (CRPS). Besides inflammation, central sensitization is also an important phenomenon. Mast cells are known to be involved in the inflammatory process of CRPS and also play a role (at least partially) in the process of central sensitization. In the development of a more mechanism‐based treatment, influencing the activity of mast cells might be important in the treatment of CRPS. We describe the rationale for using medication that counteracts the effects of mast cells in the treatment of CRPS.

Adherence to Pharmacological Pain Therapy in Patients with NonMalignant Pain: The Role of Patients' Knowledge of Pain Medication

Nonadherence to pharmacological therapy is a common and underexposed problem in patients with chronic nonmalignant pain. It may lead to treatment failure and increased healthcare costs.

Diagnostic criteria in patients with complex regional pain syndrome assessed in an out‐patient clinic

Background: Specific criteria have been described and accepted worldwide for diagnosing patients with complex regional pain syndrome (CRPS). Nevertheless, a clear‐cut diagnosis cannot be confirmed in a number of cases.

Burst Spinal Cord Stimulation in a Patient with Complex Regional Pain Syndrome: A 2-year Follow-Up

Spinal cord stimulation (SCS) is an effective therapy to treat most patients with complex regional pain syndrome (CRPS); however, the effect is not always maintained over time. We present a case report of a patient successfully treated with burst SCS after a diminishing effect of conventional tonic stimulation.

Randomized Sham-controlled Double-Blind Multicenter Clinical Trial to Ascertain the Effect of Percutaneous Radiofrequency Treatment for Sacroiliac Joint Pain: Three-month Results

Objectives:To investigate the effect of a percutaneous radiofrequency (RF) heat lesion compared with a sham procedure, applied to the lateral branches of L5, S1, S2, S3, and S4 nerve roots. Materials and Methods:Sixty patients aged 18 years and above with a medical history and physical examination suggestive for sacroiliac joint pain and a reduction of 2 or more on a numerical rating scale (NRS, 0 to 10) after a sacroiliac joint test block were included in this study. Treatment group: percutaneous RF heat lesion at the lateral branches of S1, S2, S3, and S4 nerve roots and the posterior ramus dorsalis of L5; sham group: same procedure as the treatment group except for the RF heat lesion. Primary outcome measure: pain reduction (NRS). Secondary outcome measure: Global Perceived Effect. Results:No statistically significant differences in pain level over time between the groups (Group×Period) (F1,58=0.353; P=0.56) nor within the treatment Group (F1,58=0.212; P=0.65) were found. The Period factor, however, yielded a significant difference (F1,58=61.67; P<0.001), that is, when pooled together the mean pain level of the patients was significantly reduced at T1 compared with T0. In the crossover group, 42.1% experienced a reduction in NRS of 2 or more at 1 month (P=0.65). No statistically significant difference in satisfaction over time between the groups was found (F1,50=2.1; P=0.15). The independent factors Group (F1,50=2.02; P=0.16) and Period (F1,50=0.95; P=0.33) also showed no statistically significant difference. The same applies to recovery: no statistically significant Group×Period effect (F1,51=0.09; P=0.77) was found, neither an effect of Group (F1,51=0.004; P=0.95) nor of Period (F1,51=0.27; P=0.60). Discussion:The hypothesis of no difference in pain reduction or in Global Perceived Effect between the treatment and sham group cannot be rejected. Level of Evidence:Level 1A.