Pain is the dominant symptom in osteoarthritis (OA) and sensitization may contribute to the pain severity. This study investigated the role of sensitization in patients with painful knee OA by measuring (1) pressure pain thresholds (PPTs); (2) spreading sensitization; (3) temporal summation to repeated pressure pain stimulation; (4) pain responses after intramuscular hypertonic saline; and (5) pressure pain modulation by heterotopic descending noxious inhibitory control (DNIC). Forty-eight patients with different degrees of knee OA and twenty-four age- and sex-matched control subjects participated. The patients were separated into strong/severe (VAS>or=6) and mild/moderate pain (VAS<6) groups. PPTs were measured from the peripatellar region, tibialis anterior (TA) and extensor carpi radialis longus muscles before, during and after DNIC. Temporal summation to pressure was measured at the most painful site in the peripatellar region and over TA. Patients with severely painful OA pain have significantly lower PPT than controls. For all locations (knee, leg, and arm) significantly negative correlations between VAS and PPT were found (more pain, more sensitization). OA patients showed a significant facilitation of temporal summation from both the knee and TA and had significantly less DNIC as compared with controls. No correlations were found between standard radiological findings and clinical/experimental pain parameters. However, patients with lesions in the lateral tibiofemoral knee compartment had higher pain ratings compared with those with intercondylar and medial lesions. This study highlights the importance of central sensitization as an important manifestation in knee OA.

In September 2006, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex and gender; and (3) what are the crucial questions to address in the near future? The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. We intend this document to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?" Keywords Sex differences; Gonadal hormones; Estrogens The case for studying sex and gender differences in pain and analgesiaThe pain field has moved from debating whether sex differences in pain exist to recognizing the importance of these differences. Attention is now directed toward understanding (1) what conditions lead to the expression of sex and gender differences in pain experience and reactivity, (2) what mechanisms underlie these differences, and (3) how these differences can inform clinical management of pain.As noted in a recent review, at least 79% of animal studies published in Pain over the preceding 10 years included male subjects only, with a mere 8% of studies on females only, and another 4% explicitly designed to test for sex differences (the rest did not specify) [142]. Given the substantially greater prevalence of many clinical pain conditions in women vs. men [20,199], and growing evidence for sex differences in sensitivity to experimental pain and to analgesics [21,41,213], we recommend that all pain researchers consider testing their hypotheses in both sexes, or if restricted by practical considerations, only in females. It is invalid to assume that data obtained in male subjects will generalize to females, and the best non-human model of the modal human pain sufferer -a woman -is a female animal. If only males are examined in a given study, it is important that a rationale for exclusion of females be provided and that the potential limitation in generalizability of the findings be addressed in the discussion, particularly when examining a pain phenomenon that occurs with greater prevalence or severity in females. In both preclinical and clinical studies, a comparison of both sexes will further our understanding of individual differences in sensitivity to pain and analgesia, thus improving our ability to treat and prevent pain in all people. General considerationsTwo issues of terminology are important. First, the term "sex" refers to biologically based differences, while the term "gender" refers to socially based phenomena. Although biological sex exerts a major influence on one's gender identity, sex and gender a...

Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation. Significance Central sensitisation is an important manifestation involved in many different chronic pain conditions. Central sensitisation can be different to assess and evaluate as the manifestations vary from pain condition to pain condition. Understanding central sensitisation may promote better profiling and diagnosis of pain patients and development of new regimes for mechanism based therapy. Some of the mechanisms underlying central sensitisation can be translated from animals to humans providing new options in development of therapies and profiling drugs under development.

Objective: To develop evidence-based recommendations for the management of fibromyalgia syndrome. Methods: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords ''fibromyalgia'', ''treatment or management'' and ''trial''. Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. Results: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and ''other pharmacological'' and exercise, cognitive behavioural therapy, education, dietary interventions and ''other non-pharmacological''. In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. Conclusions: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.Fibromyalgia syndrome (FMS) is a common rheumatological condition characterised by chronic widespread pain and reduced pain threshold, with hyperalgesia and allodynia. Associated features include fatigue, depression, anxiety, sleep disturbance, headache, migraine, variable bowel habits, diffuse abdominal pain and urinary frequency. Although effective treatments are available 12-14 no guidelines exist for the management of FMS. The objectives were to ascertain the strength of the research evidence on the effectiveness of treatment of FMS and develop recommendations for its management based on the best available evidence and expert opinion to inform healthcare professionals. METHODS ParticipantsA multidisciplinary taskforce was formed consisting of 19 experts in FMS representing 11 European countries. Search strategyA systematic search of Medline, PubMed, EmBASE, PsycINFO, CINAHL, Web of Sciences, Science Citation Indices, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews using the keywords: ''fibromyalgia'', ''treatment or management'' and ''trial'' for all publications till the end of December 2005 was carried out. A manual search of the bibliographies of trials was undertaken to...

In patients with knee osteoarthritis who were eligible for unilateral total knee replacement, treatment with total knee replacement followed by nonsurgical treatment resulted in greater pain relief and functional improvement after 12 months than did nonsurgical treatment alone. However, total knee replacement was associated with a higher number of serious adverse events than was nonsurgical treatment, and most patients who were assigned to receive nonsurgical treatment alone did not undergo total knee replacement before the 12-month follow-up. (Funded by the Obel Family Foundation and others; MEDIC ClinicalTrials.gov number, NCT01410409.).

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The aim of this Review is to give a short presentation of the manifestations, assessment methods, and mechanisms underlying localized and widespread musculoskeletal pain, deep somatic tissue hyperalgesia and chronification. Hyperalgesia can be explained by increased pain sensitivity of nociceptors located in deep tissue (peripheral sensitization) or by increased responses from dorsal horn neurons (central sensitization). The spreading of pain and sensitization is related to increased synaptic activity in central neurons and to changes in descending control from supraspinal centers. Manifestations related to the different aspects of sensitization can be assessed quantitatively using sensory tests, such as pressure algometry (quantitative palpation) and cuff-algometry. Repeated pressure stimulation can evaluate the degree of temporal summation, which is a proxy for the level of central sensitization, as is expanded referred muscle pain area. The transition of acute localized musculoskeletal pain into chronic widespread pain is related to the progression of peripheral and central sensitization. This sensitization for the chronification of pain should be assessed by adequate pain biomarkers. Furthermore, pain prevention should target early intervention strategies and new anti-hyperalgesic compounds should be developed.

Objective. The modest association between radiographic joint damage and pain in osteoarthritis (OA) has led to the suggestion of facilitated central pain processing. This study evaluated the importance of ongoing tissue pathology in the maintenance of enhanced central pain processing.Methods. Pain assessment was performed on 48 patients with symptomatic knee OA and 21 sex-and age-matched pain-free healthy control subjects. Twenty of the OA patients subsequently underwent total knee replacement surgery and were reassessed. Pressurepain thresholds (PPTs) were recorded using a pressure algometer (both over and distant from the knee) and a double-chamber inflatable cuff mounted around the calf. Spatial summation was assessed by relating PPTs using the dual-and single-chamber cuff. Conditioned pain modulation (CPM) was assessed by recording the increase in PPT in response to experimental arm pain.Results. PPTs at the knee and at sites away from the knee were reduced in OA patients as compared with healthy pain-free control subjects (P < 0.0001). Cuff PPTs were decreased in OA patients as compared with the healthy controls (P < 0.05), who also exhibited a greater degree of spatial summation (P < 0.05). Whereas an elevation of PPTs was noted in the healthy controls in response to experimental arm pain (P < 0.0001), no such CPM was observed in the OA patients. Following joint replacement in the OA patients, there was a reduction in the widespread mechanical hyperesthesia, along with normalization of spatial summation ratios and restoration of CPM.Conclusion. The widespread hyperesthesia and enhanced spatial summation observed in OA patients imply sensitized central pain mechanisms together with the loss of CPM. Normalization of the results following joint replacement implies that these central pain processes are maintained by peripheral input.