I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.

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Central sensitization: implications for the diagnosis and treatment of pain.

Introduction: The Danish National Patient Register (NPR) was established in 1977, and it is considered to be the finest of its kind internationally. Content: At the onset the register included information on inpatient in somatic wards. The content of the register has gradually been expanded, and since 2007 the register has included information on all patients in Danish hospitals. Validity and coverage: Although the NPR is overall a sound data source, both the content and the definitions of single variables have changed over time. Changes in the organisation and provision of health services may affect both the type and the completeness of registrations. Conclusion: The NPR is a unique data source. Researchers using the data should carefully consider potential fallacies in the data before drawing conclusions.

https://journals.sagepub.com/doi/pdf/10.1177/1403494811401482

The Danish National Patient Register

Infectious Diseases Society of America.

Motivational Interviewing: Preparing People for Change

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.

Sensitization in patients with painful knee osteoarthritis.

BackgroundMore than 670,000 total knee replacements are performed annually in the United States; however, high-quality evidence to support the effectiveness of the procedure, as compared with nonsurgical interventions, is lacking. MethodsIn this randomized, controlled trial, we enrolled 100 patients with moderate-to-severe knee osteoarthritis who were eligible for unilateral total knee replacement. Patients were randomly assigned to undergo total knee replacement followed by 12 weeks of nonsurgical treatment (total-knee-replacement group) or to receive only the 12 weeks of nonsurgical treatment (nonsurgical-treatment group), which was delivered by physiotherapists and dietitians and consisted of exercise, education, dietary advice, use of insoles, and pain medication. The primary outcome was the change from baseline to 12 months in the mean score on four Knee Injury and Osteoarthritis Outcome Score subscales, covering pain, symptoms, activities of daily living, and quality of life (KOOS4); scores range fr...

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A Randomized, Controlled Trial of Total Knee Replacement.

Patients with knee osteoarthritis demonstrate decreased pressure pain thresholds (PPTs), facilitated temporal summation (TS) of pain, and decreased conditioned pain modulation (CPM) compared with healthy controls. This study aimed to correlate preoperative PPTs, TS, and CPM with the development of chronic postoperative pain after total knee replacement (TKR) surgery. Knee pain intensity (visual analog scale [VAS]: 0-10), PPTs, TS, and CPM were collected before, 2 months, and 12 months after TKR. Patients were divided into a low-pain (VAS < 3) and a high-pain (VAS ≥ 3) group based on their VAS 12 months after TKR. The high-pain group (N = 17) had higher pain intensities compared with the low-pain group (N = 61) before surgery (P = 0.009) and 12 months after surgery (P < 0.001). The PPTs of the low-pain groups were normalized for all measurement sites comparing presurgery with 12 months postsurgery (P < 0.05, contralateral arm: P = 0.059), which was not the case for the high-pain group. The low-pain group showed a functional inhibitory CPM preoperatively and 12 months postoperatively (P < 0.05), which was not found in the high-pain group. The high-pain group had higher facilitated TS preoperatively and 12 months postoperatively compared with the low-pain group (P < 0.05). Preoperative TS level correlated to 12-month postoperative VAS (R = 0.240, P = 0.037). Patients who developed moderate-to-severe pain had pronociceptive changes compared with patients who developed mild pain postsurgery. Preoperative TS level correlated with the postoperative pain intensity and may be a preoperative mechanistic predictor for the development of chronic postoperative pain in patients with osteoarthritis after TKR.

Presurgical assessment of temporal summation of pain predicts the development of chronic postoperative pain 12 months after total knee replacement.

Pain and sensitization are major issues in patients with osteoarthritis both before and after total knee arthroplasty (TKA) and revision TKA (re-TKA). The aim of this study was to assess sensitization in patients with and without chronic pain after re-TKAs. Twenty patients with chronic knee pain and 20 patients without pain after re-TKA participated. Spreading of pain was evaluated as the number of pain sites using a region-divided body chart. The pressure pain threshold (PPT) and pressure pain tolerance (PTT) were assessed by cuff algometry at the lower leg. Temporal summation of pain was assessed by recordings of the pain intensity on a visual analog scale (VAS) during repeated cuff pressure stimulations. Conditioning pain modulation (CPM) was recorded by experimental tonic arm pain by cuff pressure stimulation and assessment of PPTs on the knee, leg, and forearm using handheld pressure algometry. Participants with pain after re-TKA compared to participants without pain demonstrated: (1) significantly more pain sites (P=.004), (2) decreased cuff PPTs and PTTs at the lower leg (P<.001), (3) facilitated temporal summation (P<.001), and (4) impaired CPM (P<.001). Additionally, significant correlations between knee pain intensity and cuff PPTs, temporal summation, and CPM and between total duration of knee pain and temporal summation were found (P<.05). This study demonstrated widespread sensitization in patients with pain after re-TKA and highlighted the importance of ongoing nociceptive input for the chronification process. This has important implications for future revisions, and precautions should be taken if patients have widespread sensitization.

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Widespread sensitization in patients with chronic pain after revision total knee arthroplasty

Recent studies indicate that the hamstrings are essen tial antagonists in ACL deficient patients. In order to evaluate muscle coordination under physiologic condi tions, nine patients with arthroscopically verified total ACL ruptures were compared with nine control volun teers. This comparison was made from electromy ograms of the thigh muscles and heel contact record ings made while walking on a treadmill.While walking on a horizontal level, the patient's muscle activity did not differ from controls, but when the knee load was increased by walking uphill, the hamstring muscles in patients were activated signifi cantly earlier than among controls. It is proposed that an altered muscle coordination is probably essential in ACL deficient patients to secure knee stability. This study suggests a new approach to investigate the coordination of muscles under physiologic conditions in ACL deficient patients, and may guide rehabilitation programs in the future.

Ole Simonsen

Papers

Sensitization in patients with painful knee osteoarthritis.

A Randomized, Controlled Trial of Total Knee Replacement.

Presurgical assessment of temporal summation of pain predicts the development of chronic postoperative pain 12 months after total knee replacement.

Widespread sensitization in patients with chronic pain after revision total knee arthroplasty

Altered timing of hamstring muscle action in anterior cruciate ligament deficient patients.