[Nondermatomal somatosensory deficits in chronic pain patients]

Nondermatomal somatosensory deficits (NDSDs) are frequently found in chronic pain patients and allude to pain sensitization and pain centralization. In the clinical examination NDSDs are as a rule accompanied by hyposensitivity to touch and heat perception often with a quadrantal or hemibody distribution. The majority of NDSD patients show a trigger episode with a somatic nociceptive trauma in the case history. These somatic findings, however, never fully explain the pain disorder, analogue to the complex regional pain syndrome (CRPS). Most patients with chronic pain disorders as well as those with NDSD often report an antecedent period of high psychobiological stress. The data from functional imaging reveal a complex pattern of a central nervous dysregulation.

[Abdominal pain - differential diagnoses and diagnostic strategies in patients with chronic symptoms]

Abdominal pain is a very common complaint in a primary care consultation. The causes of abdominal pain are extremely diverse and range from conditions that require urgent surgical remedy to those without serious underlying pathology where the problem either settles spontaneously, or becomes chronic without any abnormalities on laboratory or clinical workup. While tests are helpful in confirming diagnoses, clinical judgement based on a careful history and physical examination remains extremely important in choosing from the extremely wide differential diagnoses and in the management of the condition. In this article, we will deal with chronically recurrent intermittent abdominal pain. Our aim is especially to provide guidance on the possibility that abdominal pain is a symptom of chronic inflammatory bowel disease (IBD) or an identifiable functional condition and when the diagnosis of irritable bowel syndrome should be made.

[Chronic pain - new therapeutic strategies]

Patient suffering from chronic pain need treatment in a multimodal setting. Enriched environment might be a new therapeutical approach.

Chronic Pelvic Pain Syndrome in Men is Associated with Reduction of Relative Gray Matter Volume in the Anterior Cingulate Cortex Compared to Healthy Controls

Although chronic pelvic pain syndrome impairs the life of millions of people worldwide, the exact pathomechanisms involved remain to be elucidated. As with other chronic pain syndromes, the central nervous system may have an important role in chronic pelvic pain syndrome. Thus, we assessed brain alterations associated with abnormal pain processing in patients with chronic pelvic pain syndrome.

Nondermatomal somatosensory deficits in chronic pain patients: are they really hysterical?

Patients with chronic pain disorders frequently show nondermatomal somatosensory deficits (NDSDs) that are considered to be functional. Typically, NDSDs show quadratomal or hemibody distribution ipsilateral to the areas of chronic pain. According to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition and the International Classification of Diseases, 10th revision, such functional somatosensory deficits are classified in the chapter "conversion disorder." Many publications also used the term "hysterical sensory loss." However, doubts are increasing about this one-sided psychiatric view. We aimed to better characterize the biopsychosocial factors associated with NDSDs. Therefore, we compared 2 groups of inpatients with chronic pain disorder, of whom 90 suffered from NDSDs and 90 did not. The patients with NDSDs all showed widespread somatosensory deficits with hemibody distribution. On logistic regression analysis, history of a prior physical trauma was positively predictive for patients with NDSDs. Personality disorder and adverse childhood experiences were positively predictive for the control group with chronic pain disorders without NDSDs. The frequencies of comorbid depression and anxiety disorder did not differ statistically between groups. In conclusion, pain patients with NDSDs are, psychopathologically, by no means more noticeable personalities than patients with chronic pain disorder without NDSDs. Similar to complex regional pain syndromes, we assume a multifactorial etiology of NDSDs, including stress. Based on our observations, terms like "hysteric" should not be applied any longer to patients with NDSDs who suffer from chronic pain.

The multicenter trial SAKK 37/95 of cladribine, cyclophosphamide and prednisone in the treatment of chronic lymphocytic leukemias and low-grade non-Hodgkin's lymphomas

A multicenter trial was performed to confirm the therapeutic efficacy and the toxicity profile of the combination of cladribine, cyclophosphamide and prednisone in low-grade non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Twenty-three adults with previously treated (61%) or untreated (39%) NHL International Working Formulation A or Binet B and C CLL were administered cladribine 0.1 mg/kg/day as a subcutaneous bolus for 5 days, intravenous cyclophosphamide 500 mg/m2 on day 1, and oral prednisone 40 mg/m2 on days 1-5, every 4 weeks. Unexpected early hematological toxicities led to dose modifications for pretreated patients who received cladribine for 3 days only up to a maximum of five courses. Responses were observed in 75%, with 7 patients obtaining a complete clinical and hematological response. Median duration of complete response was 9 months. Median time to progression or relapse was 31 months. Myelosuppression and infections were dose limiting whereas posttreatment complications, including fatalities, resulted from infections. Median overall survival time from trial entry was 60 months. Activity of the combination of cladribine, cyclophosphamide and prednisone was confirmed. However, in the specific setting of a multicenter trial, unexpected fatal infectious episodes occurred in pretreated patients. Great caution is thus required in these susceptible patients and the routine use of corticosteroids should probably be abandoned.

Central hypersensitivity in chronic pain: mechanisms and clinical implications

The available literature consistently shows increased pain sensitivity after sensory stimulation of healthy tissues in patients who have various chronic pain conditions. This indicates a state of hypersensitivity of the CNS that amplifies the nociceptive input arising from damaged tissues. Experimental data indicate that central hypersensitivity is probably induced primarily by nociceptive input arising from a diseased tissue. In patients, imbalance of descending modulatory systems connected with psychologic distress may play a role. There is experimental support in animal studies for the persistence of central hypersensitivity after complete resolution of tissue damage. This is particularly true for neuropathic pain conditions, whereby potentially irreversible plasticity changes of the CNS have been documented in animal studies. Whether such changes are present in musculoskeletal pain states is at present uncertain. Despite the likely importance of central hypersensitivity in the pathophysiology of chronic pain, this mechanism should not be used to justify the lack of understanding on the anatomic origin of the pain complaints in several pain syndromes, which is mostly due to limitations of the available diagnostic tools. Treatment strategies for central hypersensitivity in patients have been investigated mostly in neuropathic pain states. Possible therapy modalities for central hypersensitivity in chronic pain of musculoskeletal origin are largely unexplored. The limited evidence available and everyday practice show, at best, modest efficacy of the available treatment modalities for central hypersensitivity. The gap between basic knowledge and clinical benefits remains large and should stimulate further intensive research.

Neurokinin-2 receptor levels correlate with intensity, frequency, and duration of pain in chronic pancreatitis

OBJECTIVE: Generation and maintenance of pain in chronic pancreatitis (CP) have been shown to be partially attributable to neuroimmune interactions, which involve neuropeptides such as substance P (SP). So far, expression of SP receptors NK-2R, NK-3R, the SP-encoding gene preprotachykinin A (PPT-A), and the SP degradation enzyme neutral endopeptidase (NEP) and their relation to pain in CP have not been determined. METHODS: Tissue samples from patients with CP (n = 25) and from healthy donors (n = 20) were analyzed for PPT-A, NK-2R, NK-3R, and NEP expression using quantitative RT-PCR. NEP protein levels were examined by immunoblot analysis and its localization was determined using immunohistochemistry. A scoring system was used to grade the extent of fibrosis on hematoxylin and eosin- and Masson-Trichrome-stained sections. Messenger RNA levels and the extent of pain were analyzed for correlations. RESULTS: In CP tissues, NK-2R and PPT-A expression was increased, whereas NK-3R and NEP mRNA levels were comparable with normal pancreas. Overexpression of NK-2R was related to the intensity, frequency, and duration of pain in CP patients. NK-1R and NEP expression was significantly related to the extent of fibrosis. CONCLUSIONS: Expression of NK-2R and PPT-A is increased in CP and is associated with pain. Failure to up-regulate NEP may contribute to the disruption of the neuropeptides loop balance in CP and thus may exacerbate the severe pain syndrome.

Ultrasound-guided blocks for the treatment of chronic pain

Ultrasound (US) is an emerging imaging technique in interventional pain management. The main advantages are the identification of soft tissues, vessels, and nerves, without exposing patients and personnel to radiation, the possibility to perform continuous imaging, and the visualization of the fluid injected in a real-time fashion. Possible applications are nerve blocks of the cervical and lumbar zygapophysial joints, stellate ganglion block, intercostal nerve blocks, occipital nerve blocks, blocks of the inguinal nerves, peripheral nerve blocks of the extremities, blocks of painful stump neuromas, caudal epidural injections, and injections of tender points. US may also be used for destructive procedures, such as cryoanalgesia, radiofrequency lesions, or chemical neurolysis. The increasing published data available suggest that US has a potential usefulness in interventional pain management, but also limitations. There is still a need for clinical trials investigating efficacy and safety of US-guided pain procedures. Until these studies are made, fluoroscopy or computed tomography remain the gold standard for most interventional pain procedures.

Psychologic factors are related to some sensory pain thresholds but not nociceptive flexion reflex threshold in chronic whiplash

OBJECTIVES: Sensory hypersensitivity, central hyperexcitability [lowered nociceptive flexion reflex (NFR) thresholds], and psychologic distress are features of chronic whiplash. However, relationships between these substrates are not clear. This study tested the hypothesis that psychologic distress and catastrophization are correlated with sensory hypersensitivity and NFR responses in chronic whiplash. METHODS: Pressure and thermal pain thresholds (mean values across 3 body sites), NFR threshold, and pain at threshold Visual Analog Scale were measured in 30 participants with chronic whiplash and 30 asymptomatic controls. Pain and disability levels Neck Disability Index, psychologic distress (GHQ-28), and catastrophization (PCS) were also measured in the whiplash group. RESULTS: Whiplash injured participants demonstrated lowered pain thresholds to pressure and cold (P<0.05); lowered NFR thresholds (P=0.003), and demonstrated above threshold levels of psychologic distress (GHQ-28) and levels of catastrophization comparable with other musculoskeletal conditions. There were no group differences for heat pain thresholds or pain at NFR threshold. In the whiplash group, PCS scores correlated moderately with cold pain threshold (r=0.51, P=0.01). In contrast, there were no significant correlations between GHQ-28 scores and pain threshold measures or between psychologic factors and NFR responses in whiplash participants. There were no significant correlations between psychologic factors and pain thresholds or NFR responses in controls. DISCUSSION: We have demonstrated that psychologic factors have some association with sensory hypersensitivity (cold pain threshold measures) in chronic whiplash but do not seem to influence spinal cord excitability. This suggests that psychologic disorders are important, but not the only, determinants of central hypersensitivity in whiplash patients.

Nondermatomal somatosensory deficits in patients with chronic pain disorder: clinical findings and hypometabolic pattern in FDG-PET

Patients with chronic pain disorders often show somatosensory disturbances that are considered to be functional. This paper aims at a more precise clinical description and at a documentation of functional neuroimaging correlates of this phenomenon. We examined 30 consecutive patients with unilaterally accentuated chronic pain not explained by persistent peripheral tissue damage and ipsilateral somatosensory disturbances including upper and lower extremities and trunk. The patients were assessed clinically and with conventional brain CT or MRI scan. In the last 11 patients functional neuroimaging was carried out (18-fluordeoxyglucose positron emission tomography=FDG-PET). Depressive symptoms were assessed with the Hamilton depression scale (HAMD-17) and pain intensity was rated with a visual analogue scale for pain (VAS). All patients suffered from mild to moderate depressive symptoms. All patients had experienced a prolonged antecedent phase of severe emotional distress; most of them remembered a "trigger episode of somatic pain" on the affected side. Somatosensory deficits were a replicable hyposensitivity to touch and heat perception of nondermatomal distribution. Conventional imaging procedures (brain CT or MRI scans) showed no structural changes. However, in 11 patients functional imaging with FDG-PET showed a significant hypometabolic pattern of changes in cortical and subcortical areas, mainly in the post-central gyrus, posterior insula, putamen, and anterior cingulate cortex. In summary, pain-related nondermatomal somatosensory deficits (NDSDs) are a phenomenon involving biological as well as psychosocial factors with replicable neuroperceptive clinical findings and a complex neurodysfunctional pattern in the FDG-PET.