Generalized expansion of nociceptive reflex receptive fields in chronic pain patients

Widespread central hypersensitivity is present in chronic pain and contributes to pain and disability. According to animal studies, expansion of receptive fields of spinal cord neurons is involved in central hypersensitivity. We recently developed a method to quantify nociceptive receptive fields in humans using spinal withdrawal reflexes. Here we hypothesized that patients with chronic pelvic pain display enlarged reflex receptive fields. Secondary endpoints were subjective pain thresholds and nociceptive withdrawal reflex thresholds after single and repeated (temporal summation) electrical stimulation. 20 patients and 25 pain-free subjects were tested. Electrical stimuli were applied to 10 sites on the foot sole for evoking reflexes in the tibialis anterior muscle. The reflex receptive field was defined as the area of the foot (fraction of the foot sole) from which a muscle contraction was evoked. For the secondary endpoints, the stimuli were applied to the cutaneous innervation area of the sural nerve. Medians (25-75 percentiles) of fraction of the foot sole in patients and controls were 0.48 (0.38-0.54) and 0.33 (0.27-0.39), respectively (P=0.008). Pain and reflex thresholds after sural nerve stimulation were significantly lower in patients than in controls (P<0.001 for all measurements). This study provides for the first time evidence for widespread expansion of reflex receptive fields in chronic pain patients. It thereby identifies a mechanism involved in central hypersensitivity in human chronic pain. Reverting the expansion of nociceptive receptive fields and exploring the prognostic meaning of this phenomenon may become future targets of clinical research.

[Characteristics of patients suffering from chronic pain with depressive symptoms in three different treatment settings]

Only few studies considered demographic and medical characteristics of pain patients with depressive symptoms.

[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.

[Chronic pain - new therapeutic strategies]

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

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.

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.

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.

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.

The prevalence of widespread central hypersensitivity in chronic pain patients

BACKGROUND Chronic pain is associated with generalized hypersensitivity and impaired endogenous pain modulation (conditioned pain modulation; CPM). Despite extensive research, their prevalence in chronic pain patients is unknown. This study investigated the prevalence and potential determinants of widespread central hypersensitivity and described the distribution of CPM in chronic pain patients. METHODS We examined 464 consecutive chronic pain patients for generalized hypersensitivity and CPM using pressure algometry at the second toe and cold pressor test. Potential determinants of generalized central hypersensitivity were studied using uni- and multivariate regression analyses. Prevalence of generalized central hypersensitivity was calculated for the 5th, 10th and 25th percentile of normative values for pressure algometry obtained by a previous large study on healthy volunteers. CPM was addressed on a descriptive basis, since normative values are not available. RESULTS Depending on the percentile of normative values considered, generalized central hypersensitivity affected 17.5-35.3% of patients. 23.7% of patients showed no increase in pressure pain threshold after cold pressor test. Generalized central hypersensitivity was more frequent and CPM less effective in women than in men. Unclearly classifiable pain syndromes showed higher frequencies of generalized central hypersensitivity than other pain syndromes. CONCLUSIONS Although prevalent in chronic pain, generalized central hypersensitivity is not present in every patient. An individual assessment is therefore required in order to detect altered pain processing. The broad basic knowledge about central hypersensitivity now needs to be translated into concrete clinical consequences, so that patients can be offered an individually tailored mechanism-based treatment.

Traumatization and chronic pain: a further model of interaction.

Up to 80% of patients with severe posttraumatic stress disorder are suffering from "unexplained" chronic pain. Theories about the links between traumatization and chronic pain have become the subject of increased interest over the last several years. We will give a short summary about the existing interaction models that emphasize particularly psychological and behavioral aspects of this interaction. After a synopsis of the most important psychoneurobiological mechanisms of pain in the context of traumatization, we introduce the hypermnesia-hyperarousal model, which focuses on two psychoneurobiological aspects of the physiology of learning. This hypothesis provides an answer to the hitherto open question about the origin of pain persistence and pain sensitization following a traumatic event and also provides a straightforward explanatory model for educational purposes.

Acute and chronic pain in calves after different methods of rubber-ring castration

The goal of the present study was to evaluate the effect of different methods of rubber-ring castration on acute and chronic pain in calves. Sixty-three 4-6 week-old calves were randomly and sequentially allocated to one of five groups: Group RR (traditional rubber ring castration); group BRR (combination of one rubber ring with Burdizzo); group Rcut (one rubber ring applied with the scrotal tissue and rubber ring removed on day 9); group 3RR (three rubber rings placed one above the other around the scrotal neck); and group CO (controls; sham-castrated). All calves received 0.2 mL/kg bodyweight lidocaine 2%, injected into the spermatic cords and around the scrotal neck 15 min before castration. The presence of acute and chronic pain was assessed using plasma cortisol concentrations, response to palpation of scrotal area, time from castration until complete wound healing, and behavioural signs. Calves of group 3RR showed severe swelling and inflammation, and licking of the scrotal area occurred significantly more often than in groups Rcut and CO. Technique 3RR was discontinued for welfare reasons before the end of the study. All castration groups had significantly more pain upon palpation than calves of group CO, but palpation elicited markedly less pain in group Rcut than in the other castration groups. The most rapid healing time and shortest duration of chronic pain after castration was achieved in group Rcut. For welfare reasons, the Rcut technique should be considered as a valuable alternative to traditional rubber ring castration of calves at 4-6 weeks of age.