Effects of Topical Application of Clonidine Cream on Pain Behaviors and Spinal Fos Protein Expression in Rat Models of Neuropathic Pain, Postoperative Pain, and Inflammatory Pain

Background: Clonidine can effectively reduce pain and/or hypersensitivity. However, the antihypersensitivity effects of clonidine topically applied in cream (CC) have not been investigated. The authors evaluated effects of topical application of CC on pain behaviors and spinal Fos-like immunoreactivity in rats with hypersensitivity.

Methods: Clonidine (30, 100, and 300 [mu]g/g) was prepared in a cream base. In rat models of neuropathic pain, inflammatory pain, and postoperative pain, the authors evaluated effects of CC (0.1 g), topically applied onto the plantar surface of the injured or uninjured paw, on thermal hyperalgesia and mechanical allodynia to von Frey filaments. The authors also evaluated effects of CC on lumbar spinal Fos-like immunoreactivity.

Results: In neuropathic rats, CC applied onto the injured paw reduced thermal hyperalgesia and mechanical allodynia dose dependently, whereas CC applied onto the uninjured paw had no effect. The antihypersensitivity effects of CC were antagonized by intraperitoneal yohimbine (10 mg/kg). Further, CC reduced Fos-like immunoreactivity in neuropathic rats. In contrast, CC in a single dose had no effects on hyperalgesia, allodynia, or Fos-like immunoreactivity in rats with inflammatory or postoperative pain. In rats with postoperative pain, CC repeatedly applied for 6 days reduced thermal hyperalgesia, but not mechanical allodynia, in the postoperative days, whereas it had no effects on hyperalgesia or allodynia in those with inflammatory pain.     

Pain, distress and joint hyperlaxity

Pain dominates the lives of many patients with hyperlaxity syndromes, most commonly the Benign Joint Hypermobility Syndrome (BJHS/EDS). As a result they may experience psychosocial problems, which in many cases severely affects their healthy functioning. Above all is the overriding chronic pain in joints, muscles and ligaments, which arises from an inherent predisposition to the effects of everyday trauma, but other factors such as associated osteoarthritis or fibromyalgia are also important. There may also be neurophysiological factors at play producing nociceptive enhancement. Pain and distress of visceral origin can result from laxity of connective tissue within or providing support for the abdominal, thoracic or pelvic viscera leading to hernia, uterine and/or rectal prolapse, mitral valve prolapse or spontaneous pneumothorax. In children joint hyperlaxity is an important (and often unrecognised) source of rheumatic symptoms, which may be ignored or erroneously ascribed to juvenile idiopathic arthritis. The management of pain and distress in the hyperlaxity syndromes requires skill, patience, compassion and understanding. Often the results of conventional anti-rheumatic therapy (including anti-rheumatic drugs and surgery) as applied to other rheumatic diseases are disappointing and innovative approaches are required. Amongst these, for which evidence of efficacy is available, are physiotherapeutic and orthotic stabilisation of hyperlax joints, proprioceptive enhancement and the newer pain management techniques including cognitive behavioural therapy.     

Pain, nociception and the developing infant

The study of paediatric pain and the provision of safe but reliable analgesia for all age groups has become a central issue in paediatric anaesthesia. For the practising paediatric anaesthetist, this represents a major challenge: the developing infant is not a single discrete entity but one that changes constantly with increasing maturity of individual organs. Recent developments in both basic and clinical sciences has given valuable insights into this process, giving the clinician a firm basis to provide analgesia at all ages. This review looks at some of the most interesting recent developments in this field.     

Pain, catastrophizing, and depression in the rheumatic diseases

Persistent and disabling pain is the hallmark of osteoarthritis, rheumatoid arthritis, fibromyalgia, and various other rheumatologic conditions. However, disease severity (as measured by 'objective' indices such as those that employ radiography or serology) is only marginally related to patients' reports of pain severity, and pain-related presentation can differ widely between individuals with ostensibly similar conditions (for example, grade 4 osteoarthritis of the knee). Increasing evidence in support of the biopsychosocial model of pain suggests that cognitive and emotional processes are crucial contributors to inter-individual differences in the perception and impact of pain. This Review describes the growing body of literature relating depression and catastrophizing to the experience of pain and pain-related sequelae across a number of rheumatic diseases. Depression and catastrophizing are consistently associated with the reported severity of pain, sensitivity to pain, physical disability, poor treatment outcomes, and inflammatory disease activity, and potentially with early mortality. A variety of pathways, from cognitive to behavioral to neurophysiological, seem to mediate these deleterious effects. Collectively, depression and catastrophizing are critically important variables in understanding the experience of pain in patients with rheumatologic disorders. Pain, depression, and catastrophizing might all be uniquely important therapeutic targets in the multimodal management of a range of such conditions.     

Pain,function, and radiographic disease in trapeziometacarpal osteoarthritis

IntroductionTrapeziometacarpal joint osteoarthritis (OA) produces significant functional impairment due to pain and loss of strength in both power and precision grips, but few studies have related radiographic scores to functional and pain-based measures.PurposeTo investigate the association between markers of radiographic disease and outcomes for symptomatic and functional disease.Study DesignThis study in an exploratory analysis of baseline data from the first 100 participants in a clinical trial evaluating the efficacy of combined conservative therapies for base of thumb OA (COMBO).MethodsFunctional Index for Hand Osteoarthritis (FIHOA) scores and Visual Analogue Scale (VAS) scores for pain were recorded for the index hand. Bilateral isometric grip and tip-pinch strength measurements were taken, as well as posteroanterior and Eaton stress-view hand radiographs. Generalized estimating equations (GEEs), univariate, and multivariate analyses were used according to whether the data were bilateral or unilateral.ResultsA total of 79 females and 21 males were included, with a median Kellgren-Lawrence (KL) grade of 3 in the index hand. Higher KL and Eaton grades were associated with lower grip strength in the GEE analysis (B-coefficients of -1.25 and -1.16, and P-values of .002 and .010, respectively). Higher KL grade was also associated with poorer function and higher pain levels in the multivariable analysis (B-coefficients of 1.029 and 3.681, and P-values of .021 and .047, respectively). Lower radial subluxation ratios were associated with lower grip strength in the GEE analysis, and higher pain scores in the multivariable analysis (B-coefficients of 2.06 and -42.1, and P-values of .006 and .031, respectively). Greater pain scores were also associated with poorer function (B-coefficient 0.082, P-value .001).ConclusionMore advanced radiographic trapeziometacarpal OA severity is associated with lower grip strength and poorer self-reported functional outcomes. Lower subluxation ratios were associated with higher pain scores and lower grip strength.     

Pain,stress and depression: Psychoneurophysiology and therapy

Depression is probably the most common illness in the world, and it is much maligned by patients and physicians as well as the insurance industry. We have found that all patients with depression have one or more chemical and neurochemical abnormalities. More importantly, we have found that 85 per cent of patients can be brought out of depression within 2 weeks without drug therapy. The therapy program consists of education, cranial electrical stimulation, music, photostimulation, insight meditation and magnesium supplments. Interestingly, videotaped education is more effective than live lectures.     

Pediatric Pain: Biological and Social Context. Progress in Pain Research and Management, Volume 26

This is Volume 26 in a series of books from the InternationalAssociation for the Study of Pain (IASP), in their series onpain management and research. The whole book is devoted to theproceedings of the 4th International Forum on Pediatric Pain,held in Nova Scotia, Canada in September 2002. This makes ita     

Pain management in end-of-life care, representations, realities and advances

Pain management is essential at every stage of a disease. At the end of life, healthcare professionals are increasingly attentive to the discomfort each treatment may cause. The recent publication of recommendations offers new perspectives with regard to situations of intractable pain.