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Background It is unknown why an acute pain condition under various circumstances can transition into a chronic pain condition. There has been a shift towards neuroinflammation and hence glial cell activations specifically in the dorsal root ganglion and spinal cord as a mechanism possibly driving the transition to chronic pain. This has led to a focus on non-neuronal cells in the peripheral and central nervous system. Besides infiltrating macrophages, Schwann cells and satellite glial cells release cytokines and therefore important mechanisms in the maintenance of pain. Activated Schwann cells, satellite glial cells, microglia, and astrocytes may contribute to pain sensitivity by releasing cytokines leading to altered neuronal function in the direction of sensitisation. Aims of this perspective paper 1) Highlight the complex but important recent achievement in the area of neuroinflammation and pain at spinal cord level and in the dorsal root ganglion. 2) Encourage further research which hopefully may provide better understanding of new key elements driving the transition from acute to chronic pain. Recent results in the area of neuroinflammation and pain Following a sciatic nerve injury, local macrophages, and Schwann cells trigger an immune response immediately followed by recruitment of blood-derived immune cells. Schwann cells, active resident, and infiltrating macrophages release proinflammatory cytokines. Proinflammatory cytokines contribute to axonal damage and also stimulate spontaneous nociceptor activity. This results in activation of satellite glial cells leading to an immune response in the dorsal root ganglia driven by macrophages, lymphocytes and satellite cells. The anterograde signalling progresses centrally to activate spinal microglia with possible up regulation of glial-derived proinflammatory/pronociceptive mediators. An important aspect is extrasegmental spreading sensitisation where bilateral elevations in TNF-α, IL-6, and IL-10 are found in dorsal root ganglion in neuropathic models. Similarly in inflammatory pain models, bilateral up regulation occurs for TNF-α, IL-1 β, and p38 MAPK. Bilateral alterations in cytokine levels in the DRG and spinal cord may underlie the spread of pain to the uninjured side. An important aspect is how the opioids may interact with immune cells as opioid receptors are expressed by peripheral immune cells and thus can induce immune signaling changes. Furthermore, opioids may stimulate microglia cells to produce proinflammatory cytokines such as IL-1. Conclusions The present perspective paper indicates that neuroinflammation and the associated release of pro-inflammatory cytokines in dorsal root ganglion and at the spinal cord contribute to the transition from acute to chronic pain. Neuroinflammatory changes have not only been identified in the spinal cord and brainstem, but more recently, in the sensory ganglia and in the nerves as well. The glial cell activation may be responsible for contralateral spreading and possible widespread sensitisation. Implications Communication between glia and neurons is proposed to be a critical component of neuroinflammatory changes that may lead to chronic pain. Sensory ganglia neurons are surrounded by satellite glial cells but how communication between the cells contributes to altered pain sensitivity is still unknown. Better understanding may lead to new possibilities for (1) preventing development of chronic pain and (2) better pain management.

Background and aim No studies have been published regarding the results of lumbar spine surgery a in population-based setting in Finland. Our objective was to investigate functional capacity and quality of life after lumbar spine surgery in a population-based cohort in Northern Finland, focusing on working-age patients. Methods This was a cross-sectional postal survey. Three questionnaires (a self-made questionnaire, the Oswestry Low Back Disability Questionnaire and the SF-36) were sent the patients aged 18-65 years who had undergone lumbar spine surgery due to disc herniation, instability or spinal stenosis in the Oulu University Hospital between June 2005 and May 2008. Results The postal survey was sent to 814 patients, of whom 537 patients (66%) replied. Of these, 361 (67%) underwent disc surgery, 85 (16%) stabilizing surgery and 91 (17%) decompression. Pain was absent or present only occasional in 51% in the disc surgery group, whereas it was present daily in 59% in the stabilizing surgery group and in 58% in the decompression group ( P < 0.001). Axial pain was slightly more intense than radicular pain. Pain was milder in the disc surgery group compared with the stabilizing surgery and decompression groups: mean (SD) axial pain with 0-10 NRS was 4.0 (2.3), 4.7 (2.4) and 4 (2.3) respectively ( P = 0.002) and radicular pain 3.5 (2.6), 4.2 (2.8), 4.5 (2.6) respectively ( P < 0.001). The total ODI score (mean, SD) was 20 (17) in the disc surgery group, 35 (17) in the stabilizing surgery group and 32 (17) in the decompression group ( P < 0.001). The physical dimension sum score from the SF-was 42 (11) in the disc surgery group and 34 (10) in the stabilizing surgery and decompression grou ( P < 0.001). Mental sum scores did not vary significantly between the groups. Conclusions and Implications Outcome was good after lumbar disc operations but less favourable after stabilizing surgery and decompression regarding pain, functional capacity and quality of life. Implications. This study offers important information about outcome after lumbar spine surgery in Oulu University Hospital. It also brings out that in Finland we need systematic national spine register, with accurate pre-and postoperative data.

Background and aims Chronic pain not only affects the person in pain, but can also have a negative impact on relationships with loved ones. Research shows that chronic pain is associated with difficulties in marital relationships, which in turn is related to a variety of negative outcomes such as psychological distress and conflict within the family. This suggests that couples where chronic physical pain is present also struggle with emotional pain and relationship problems, and thus targeting relationship skills and interpersonal functioning might be helpful for these couples. Although studies in this area are promising, their numbers are few. In the present study, validation as a way of communicating is suggested for handling emotional expression in interpersonal interactions. Validation communicates understanding and acceptance of the other person’s experience, and it has been shown to have a down-regulating effect on negative emotions. It has previously been demonstrated to be important for these couples. However, the feasibility and effects of increasing partner validation in these couples are unknown. Therefore, the aim of the present study was to investigate if a brief training session in validation for spouses would result in more validating and fewer invalidating responses towards their partners with pain, and to investigate if changes in these behavioural responses were associated with changes in emotion and pain level in the partner with pain. Methods Participants were 20 couples where at least one partner reported chronic pain. The study employed a within-groups design in which spouses of people with pain received validation training (without their partner’s knowledge), and their validating and invalidating responses were rated pre- and post-intervention using a reliable observational scale. Also, positive and negative affect and subjective pain level in the persons with pain were rated pre- and post-intervention. Results Results showed that the validation training was associated with increased validating and decreased invalidating responses in the partners. Their spouses with chronic pain reported a decrease in negative affect from pre- to post-training. Conclusions Our results indicate that the partner or closest family member, after brief validation training, increased validating responses and decreased invalidating responses towards the person with pain, which had an immediate positive impact on emotions in the other person. Implications This study suggests that using validation in interpersonal interactions is a promising tool for couples where chronic pain is present.

Background and aims Chronic pain is a life altering condition and common among elderly persons. The 7-day buprenorphine patch could be a suitable treatment for managing chronic pain of moderate severity in elderly patients in Sweden. The objective of this analysis was to investigate the cost-effectiveness of the 7-day buprenorphine patch, versus no treatment, in patients >50 years old who suffer from moderate pain in a health economic perspective. An additional aim was to evaluate how the cost-effectiveness is affected by the choice of EQ-5D weights. Methods The annual treatment cost and the potential gains in health-related quality of life (HRQoL) of buprenorphine, compared to no treatment, were evaluated. Original EQ-5D data were collected from four clinical reference studies at baseline and at the final visit. Treatment effects on HRQoL were then assessed using both UK and Swedish EQ-5D weights. Annual treatment costs were calculated based on costs of physician visits and pharmaceuticals. The optimal treatment dose was 10-15 μg/h and the analysis was hence performed on both a 10- and a 15 μg/h buprenorphine patch. Results The analysis of buprenorphine treatment resulted in improved HRQoL in all reference studies, irrespective of choice of EQ-5D weight set. The change in quality adjusted life years (QALYs) varied with a gain of 0.042-0.118 using the UK weights and 0.020-0.051 with the Swedish weights. The average annual treatment cost was SEK14454 for the 10μg/h patch and SEK17 017 for the 15 μg/h patch, while cost for the no-treatment alternative was SEK 9 960. The base case incremental cost-effectiveness ratios (ICER) with the UK weights were SEK 40000-SEK 170000 and SEK 90000-SEK 350000 when applying the Swedish weights. The corresponding ICER-span in the sensitivity analysis was SEK 15 000-SEK 400 000 when applying the UK weights and SEK 30 000-SEK 840 000 with the Swedish weights (SEK 100 is about €11). Conclusions The results imply that the 7-day buprenorphine patch may be a cost-effective treatment of moderate chronic pain in patients over 50 years of age. The UK and the Swedish EQ-5D weights generated vastly different HRQoL estimates but buprenorphine remains cost-effective regardless choice of weight set.

Background Research has emphasised the essential role of psychosocial risk factors in chronic pain. In practice, pain is usually verified by identifying its physical cause. In patients without any distinct pathology, pain is easily defined as imaginary pain. The aim of this qualitative study was to explore the invisibility of chronic pain, from the patients’ perspective. Methods Thirty-four participants with chronic pain were interviewed. The mean age of the participants was 48 years, and 19 of them were women. For 21 of the participants, the duration of pain was more than five years, and most of the participants had degenerative spinal pain. The transcribed interviews were analysed using Giorgi’s four-phase phenomenological method. Results The participants’ chronic pain was not necessarily believed by health care providers because of no identified pathology. The usual statements made by health care providers and family members indicated speculation, underrating, and denial of pain. The participants reported experience of feeling that they had been rejected by the health care and social security system, and this feeling had contributed to additional unnecessary mental health problems for the participants. As a result from the interviews, subthemes such as “Being disbelieved”, “Adolescents’ pain is also disbelieved”, “Denying pain”, “Underrating symptoms”, “The pain is in your head”, “Second-class citizen”, “Lazy pain patient”, and “False beliefs demand passivity” were identified. Conclusions In health care, pain without any obvious pathology may be considered to be imaginary pain. Despite the recommendations, to see chronic pain as a biopsychosocial experience, chronic pain is still regarded as a symptom of an underlying disease. Although the holistic approach is well known and recommended, it is applied too sparsely in clinical practice. Implications The Cartesian legacy, keeping the mind and body apart, lives strong in treatment of chronic pain despite recommendations. The biopsychosocial approach seems to be rhetoric.

Background and aims Despite the high prevalence of knee osteoarthritis (OA) it remains one of the most frequent knee disorders without a cure. Pain and disability are prominent clinical features of knee OA. Knee OA pain is typically localized but can also be referred to the thigh or lower leg. Widespread hyperalgesia has been found in knee OA patients. In addition, patients with hyperalgesia in the OA knee joint show increased pain summation scores upon repetitive stimulation of the OA knee suggesting the involvement of facilitated central mechanisms in knee OA. The dynamics of the pain system (i.e., the adaptive responses to pain) has been widely studied, but mainly from experiments on healthy subjects, whereas less is known about the dynamics of the pain system in chronic pain patients, where the pain system has been activated for a long time. The aim of this study was to assess the dynamics of the nociceptive system quantitatively in knee osteoarthritis (OA) patients before and after induction of experimental knee pain. Methods Ten knee osteoarthritis (OA) patients participated in this randomized crossover trial. Each subject was tested on two days separated by 1 week. The most affected knee was exposed to experimental pain or control, in a randomized sequence, by injection of hypertonic saline into the infrapatellar fat pad and a control injection of isotonic saline. Pain areas were assessed by drawings on anatomical maps. Pressure pain thresholds (PPT) at the knee, thigh, lower leg, and arm were assessed before, during, and after the experimental pain and control conditions. Likewise, temporal summation of pressure pain on the knee, thigh and lower leg muscles was assessed. Results Experimental knee pain decreased the PPTs at the knee ( P <0.01) and facilitated the temporal summation on the knee and adjacent muscles ( P < 0.05). No significant difference was found at the control site (the contralateral arm) ( P =0.77). Further, the experimental knee pain revealed overall higher VAS scores (facilitated temporal summation of pain) at the knee ( P < 0.003) and adjacent muscles ( P < 0.0001) compared with the control condition. The experimental knee pain areas were larger compared with the OA knee pain areas before the injection. Conclusions Acute experimental knee pain induced in patients with knee OA caused hyperalgesia and facilitated temporal summation of pain at the knee and surrounding muscles, illustrating that the pain system in individuals with knee OA can be affected even after many years of nociceptive input. This study indicates that the adaptability in the pain system is intact in patients with knee OA, which opens for opportunities to prevent development of centralized pain syndromes.

Background Trigeminal neuralgia is a neuropathic disorder characterized by episodes of intense pain in the face. Drug therapy is the first choice of treatment. However, in cases where drug therapy are contraindicated due to side effects, patients can get pain relief from lengthy neurosurgical procedures. Alternatively, a peripheral trigeminal nerve block can be easily performed in an outpatient setting. Therefore it is a useful treatment option for the acute paroxysmal period of TN in patients who cannot use drug therapy. We performed real-time ultrasound guidance for infraorbital nerve blocks in TN patients using a high concentration of tetracaine dissolved in bupivacaine. In this report, we examine the efficacy of our methods. Patients As approved by the Institutional Review Board, the medical records in our hospital were queried retrospectively. Six patients with TN at the V2 area matched the study criteria. All patients could not continue drug therapy with carbamazepine due to side effects and they received an ultrasound-guided infraorbital nerve block with a high concentration of tetracaine dissolved in bupivacaine. Methods The patient was placed in the supine position and the patient’s face was sterilized and draped. An ultrasound system with a 6-13 MHz linear probe was used with a sterile cover. The probe was inserted into the horizontal plane of the cheek just beside the nose and was slid in the cranial direction to find the dimple of the infraorbital foramen. The 25G 25 mm needle was inserted from the caudal side just across from the probe using an out-of-plane approach. To lead the needle tip to the foramen, needle direction was corrected with real-time ultrasound guidance. After the test block with lidocaine (2%, 0.5 ml), a solution of tetracaine (20 mg) dissolved in bupivacaine (0.5%, 0.5 ml) was injected. During each injection, the spread of the agent around the nerve was confirmed using ultrasound images. Results Ten blocks were performed for six patients. Immediately after the procedure, all 10 blocks produced analgesia and relieved the pain. In the three blocks, pain was experienced in a new trigger point outside of the infraorbital nerve region (around the back teeth) within a week after the block and pain were relieved using other treatment. Two patients developed small hematomas in the cheek but they disappeared in a week. All patients did not complain about other side effects including paraesthesia, hyperpathia, dysaesthesia, or double vision. Hypoaesthesia to touch and pain in the infraorbital region were observed in all blocks after 2 weeks. Conclusions We performed real-time ultrasound-guided infraorbital nerve block for TN with a high concentration of tetracaine dissolved in bupivacaine. Our method achieved a high success rate and there were only minor and transient side effects. Implications Real-time ultrasound-guided infraorbital nerve block is one of the useful options to treat the acute paroxysmal period of TN at the infraorbital nerve area. Ultrasound-guided injections may become the standard practice for injecting peripheral trigeminal nerves. Using this high concentration of tetracaine as a neurolytic agent is effective and appears to have only minor side effects.

Background and aims To our knowledge there are no studies that have examined the effects of the experimental pain on muscle fibre excitability as measured by the amplitudes of the potentials evoked by direct muscle stimulation (DMS) in a muscle at rest. We hypothesized that evoked pain can modulate the muscle compound action potential (CMAP) obtained by DMS possibly due to changes in muscle fibre excitability. Methods Pain was evoked by intramuscular infusion of hypertonic saline in 50 men. Ten control subjects were infused with isotonic saline. The infusions were given distal to the motor end plate region of the dominant brachial biceps muscle (BBM) in a double-blind manner. The nerve CMAP was obtained by stimulating the musculocutaneous nerve and recording from the BBM using surface-electrodes. Muscle CMAPs were obtained by direct muscle stimulation with subdermal electrodes placed subcutaneously in the distal third of the muscle. A stimuli-response curve of the amplitudes from muscle CMAP was obtained by stimulating from 10 to 90 mA. Results There was a decrease of the nerve CMAP amplitudes after infusion of isotonic saline (from 13.78mV to 12.16 mV), p -value 0.0007 and of hypertonic saline (from 13.35 mV to 10.85 mV), p -value 0.0000. The percent decrease from before to after infusion was larger in the hypertonic saline group (19.37%) compared to the isotonic saline group (12.18%), p -value 0.025. There was a decrease of the amplitudes of the muscle CMAP after infusion of both isotonic (at 90 mA from 13.84mV to 10.32 mV, p value 0.001) and of hypertonic saline (at 90 mA from 14.01 mV to 8.19 mV, p value 0.000). The percent decrease was larger in the hypertonic saline group compared to the isotonic saline group for all the stimulations intensities. At 90 mA we saw a 42% decrease in the hypertonic saline group and 24.5% in the isotonic saline group, p value 0.005. There were no changes in conduction velocity. Conclusion We found a larger amplitude decrease of the muscle and nerve potentials following hypertonic saline infusion compared with that of isotonic saline. We suggest that this deferential outcome of hypertonic saline on muscle CMAP may be linked to the nociceptive effect on muscle fibre membrane excitability. Implications The study supplies with some evidence of the peripheral effect of muscle pain. However, further trials with other nociceptive substances such as capsaicin should be performed.