Volume 1, Issue 3

Background Brain activation resulting from acute postoperative pain has to our knowledge not previously been studied using positron emission tomography, except from one case study. The aim of this study was to monitor activation in brain sensory pathways during acute pain after surgery of the hand. A secondary aim was to compare brain activation in clinical postoperative pain to that previously reported, by the same research group, for a model of experimental pain from the same body area. Increase in regional cerebral blood flow (rCBF) is presumed to indicate neuronal activation and decrease in blood flow decreased neuronal firing. An increase in blood flow in a brain region may represent stimulatory activity as well as inhibitory. Methods Brain activity was measured during clinical postoperative pain and a pain free state in six patients with positron emission tomography (PET) as changes in regional cerebral blood flow (rCBF). rCBF during pain from surgery of the right thumb base was compared with a pain free state achieved by regional anaesthesia of the painful area. Results In postoperative pain, patients had a significantly higher CBF in the contralateral/primary and secondary somatosensory cortices as well as in the contralateral motor cortex compared to the pain free stat during local regional anaesthesia. Relatively lower rCBF during the pain state was observed in clusters in the contralateral tertiary sensory cortex, ipsilateral and contralateral secondary visual cortex, prelimbic cortex, ipsilateral prefrontal as well as anterior cingulate cortex and contralateral secondary somatosensory cortex. The increased rCBF in primary and somatosensory cortices probably correspond to pain localizing processing. We also compared the findings in cerebral activation patterns of the postoperative pain state as described above, with the results from a previously published study by the same research group, using an experimental pain model when pain was inflicted with application of mustard oil in the same location, the thumb base region of the right hand. Since no formal statistical analysis was carried out between the two studies, the data are not very strong, but the differences reported were obvious when comparing the two situations. The comparison gave the following outcome: Digit activation occurred in identical sensory brain areas, i.e. primary and secondary somatosensory cortices, as compared to the changes in this study, supporting that pain localization processes use similar sensory pathways in a nociceptive acute experimental pain model, and in clinical acute postoperative nociceptive pain. Dissimilarities were observed between the models in activation of brain areas coding of the emotional pain qualities, indicating some differences between the experimental and “real” acute nociceptive pain. Conclusion We have reported a distinct cerebral activation pattern produced by acute postoperative pain following hand surgery. The findings were compared to data obtained in a previously published report of the cerebral activation pattern from an acute experimental pain model in volunteers. We found similarities as well as some differences in the activation pattern between the two situations.

Objective Patients with osteoarthritis (OA) pain often have insufficient pain relief from non-opioid analgesics. The aim of this trial was to study efficacy and tolerability of a low dose 7-day buprenorphine transdermal delivery system, added to a NSAID or coxib regimen, in opioid-naïve patients with moderate to severe OA pain. Methods A 6 months randomised, double-blind, parallel-group study at 19 centres in Denmark, Finland, Norway, and Sweden, in which OA patients (>40 years) with at least moderate radiographic OA changes and at least moderate pain in a hip and/or knee while on a NSAID or a coxib were randomised to a 7-day buprenorphine patch ( n = 100) or an identical placebo patch ( n = 99). The initial patch delivered buprenorphine 5 μg/h. This was titrated to 10 or 20 μg/h, as needed. Rescue analgesic was paracetamol 0.5–4 g daily. Statistical analysis of outcome data was mainly with a general linear model, with treatment as factor, the primary joint of osteoarthritis, baseline scores, and season as covariates. Results Most patients had OA-radiographic grade II (moderate) or grade III (severe), only 8 in each group had very severe OA (grade IV). The median buprenorphine dose was 10 μg/h. 31 buprenorphine-treated patients and 2 placebo-treated patients withdrew because of side effects. Lack of effect caused 12 placebo-treated and 7 buprenorphine-treated patients to withdraw. The differences in effects between treatments: Daytime pain on movement, recorded every evening on a 0–10 numeric rating scale decreased significantly more (P = 0.029) in the buprenorphine group. Patients’ Global Impression of Change at the end of the double blind period was significantly improved in the buprenorphine group (P = 0.017). The chosen primary effect outcome measure, the Western Ontario and McMaster Universities (WOMAC) OA Index for Pain (P = 0.061), and secondary outcome measures, the WOMAC OA score for functional abilities (P = 0.055), and the WOMAC total score (P = 0.059) indicated more effects from buprenorphine than placebo, but these differences were not statistically significant. In a post-hoc, subgroup analysis with the 16 patients with radiographic grad IV (very severe) excluded, WOMAC OA Index for Pain was significantly (P = 0.039) reduced by buprenorphine, compared with placebo. WOMAC OA score for stiffness and the amount of rescue medication taken did not differ. Sleep disturbance, quality of sleep, and quality of life improved in both groups. Side effects : Typical opioid side effects caused withdrawal at a median of 11 days before completing the 168 days double blind trial in 1/3 of the buprenorphine group. Mostly mild local skin reactions occurred equally often (1/3) in both groups. Conclusions Although the 24 hours WOMAC OsteoArthritis Index of pain was not statistically significantly superior to placebo, day-time movement-related pain and patients’ global impression of improvement at the end of the 6-months double blind treatment period were significantly better in patients treated with buprenorphine compared with placebo. Opioid side effects caused 1/3 of the buprenorphine-patients to withdraw before the end of the 6-months double blind study period. Implications A low dose 7-days buprenorphine patch at 5–20 μg/h is a possible means of pain relief in about 2/3 of elderly osteoarthritis patients, in whom pain is opioid-sensitive, surgery is not possible, NSAIDs and coxibs are not recommended, and paracetamol in tolerable doses is not effective enough. Vigilant focus on and management of opioid side effects are essential.

Background The antidepressant drugs imipramine and venlafaxine relieve clinical neuropathic pain and have been shown to increase pain thresholds in healthy volunteers during repetitive electrical sural nerve stimulation causing temporal pain summation, whereas pain during the cold pressor test is unaltered by these drugs. If this pattern of effect in experimental pain models reflects potential efficacy in clinical neuropathic pain, the pain summation model may potentially be used to identify new drugs for such pain conditions. Gabapentinoids are evidence-based treatments of clinical neuropathic pain and could contribute with additional knowledge of the usefulness of the pain summation model. The aim of this study To test the analgesic effect of the gabapentinoid gabapentin in a sural nerve stimulation pain model including temporal pain summation and the cold pressor test. Method 18 healthy volunteers completed a randomized, double-blind, cross-over trial with medication of 600 mg gabapentin orally dosed 3 times over 24 h against placebo. Pain tests were performed before and 24 h after medication including pain detection and tolerance to single sural nerve stimulation and pain summation threshold to repetitive stimulation (3 Hz). Peak pain intensity and discomfort were rated during a cold pressor test. Results Compared to placebo, gabapentin had a highly significant effect on the threshold of pain summation to repetitive electrical sural nerve stimulation ( P = 0.009). Gabapentin significantly increased the pain tolerance threshold to single electrical sural nerve stimulation ( P = 0.04), whereas the pain detection threshold to single electrical sural nerve stimulation tended to be increased ( P = 0.06). No significant differences were found on pain ratings during the cold pressor test. Conclusion Gabapentin had a selective hypoalgesic effect in a human experimental pain model of temporal pain summation and the results lend further support to the usefulness of the pain summation model to identify drugs for neuropathic pain.

Prevalence estimates of pain differ depending on how it is defined and measured and on the populations studied. It has been estimated that on a given day, as many as 30–44% of the general population experience some kind of pain. Information about the prevalence of pain in Iceland is not available. The aims of this study were to evaluate the prevalence of pain of various origins among the general population of Iceland, to test hypotheses regarding relationships between pain, quality of life (QOL) and demographic variables, to evaluate participants’ beliefs about causes of their pain, and to evaluate how those who experience pain manage it. A random sample of 1286 adults was drawn from a national registry holding information about all citizens of Iceland. Data were collected with a postal-survey. Pain was evaluated with the Brief Pain Inventory (BPI), with instructions modified to evaluate pain in the past week as opposed to the past 24 h. Of 1286 invited, 599 (46.6%) participated, of which, 232 had experienced pain in the past week (40.3%). Participants had a mean (SD) age of 44.94 (17.12) years and 56% were women. Those who had pain perceived their health to be worse than those who had not [ B = −0.91, SE = 0.15, Wald = 38.75, p = 0.00], but did not differ on other variables. Of 232 individuals reporting pain, 183 (79.6%) or 30.6% of the total sample had experienced pain for more than three months. On a scale from 0 “no pain” to 10 “pain as bad as I can imagine” the mean (SD) pain severity score (composite of four pain severity scores) for the 232 participants reporting pain was 3.21 (1.73) and pain interference with life activities 2.59 (1.98), also on a 0–10 scale. Pain severity predicted pain interference [ B = 0.71; F = 126.14; df = 1,206; p = 0.00], which mediated the effects of pain severity on mood and QOL. Between Pain Interference with Life and Positive Affect [ B = −0.06; F = 4.53; df = 1,196; p = 0.04], between Pain Interference and Negative Affect [ B = 0.15; F = 23.21; df = 1,196; p = 0.00], and between Pain Interference and Global Quality of Life [ B = −0.18; F = 29.11; df = 1,196; p = 0.00]. Most frequent causes for pain were strain injuries ( n = 79), resulting from work or sports activity, arthritis ( n = 39), mechanical problems (e.g. due to birth defects, curvature, slipped discs, etc.) ( n = 37), various diseases ( n = 31) and accidents ( n = 30). Nineteen participants did not know what caused their pain. Treatments for pain varied, but most had used medications alone ( n = 76) or in combination with other treatments ( n = 61). The prevalence of pain in the general population of Icelandic adults is similar to what has been reported. Estimates of chronic pain are towards the higher end when compared to data from other European counties, yet comparable to countries such as Norway. This raises questions about possible explanations to be looked for in genetics or cultural point of view. This population based study provides valuable information about the prevalence of pain in Iceland and also supports findings previously reported about pain in the neighboring countries.

Objective Health care providers, especially registered nurses (RNs), are a professional group with a high risk of musculoskeletal pain (MSP). This longitudinal study contributes to the literature by describing the prevalence and change in MSP, work-related factors, personal factors, self-reported pain, disability and sick leave (>7 days) among RNs working in a Swedish hospital over a 3-year period. Further, results concerning prediction of pain, disability and sick leave from baseline to a 3-year follow-up are reported. Method In 2003, a convenience sample of 278 RNs (97.5% women, mean age 43 years) completed a questionnaire. In 2006, 244 RNs (88% of the original sample) were located, and 200 (82%) of these completed a second questionnaire. Results Logistic regression analyses revealed that pain, disability and sick leave at baseline best predicted pain, disability, and sick leave at follow-up. The personal factors self-rated health and sleep quality during the last week predicted pain at follow-up, while age, self-rated health, and considering yourself as optimist or pessimist predicted disability at follow-up, however weakly. None of the work-related factors contributed significantly to the regression solution. Conclusions The results support earlier studies showing that a history of pain and disability is predictive of future pain and disability. Attention to individual factors such as personal values may be needed in further research.

Objectives Women report more musculoskeletal pain than men. A dysfunctional pain inhibitory system has been launched as a contributing factor for these gender differences. This study used a diffuse noxious inhibitory controls (DNIC) paradigm and asked the following questions: (1) is electrically induced muscle pain inhibited by a painful heat stimulus to the forearm, and (2) does women show signs of reduced inhibition compared to men?. Methods Forty healthy subjects (20 females; 18–45 years) participated in a cross-over design with painful (45–49 °C) or non-painful (35 °C) conditioning heat stimuli (in balanced order) to the contralateral forearm. The subjects received 10 painful electrical stimuli in the tibialis anterior muscle before, during and after conditioning and rated each electrical stimulus on a 0–10cm visual analogue scale (VAS). There was 30 min between experiments. All VAS scores were normalized to scores before conditioning (100%) and analyzed by RM-ANOVA. Females participated during the ovulatory phase (days 12–14). Results There was a main effect of conditioning. VAS scores during conditioning were reduced to 90 ± 24% (mean ± S.D.) with respect to before conditioning ( p = 0.02). There was no difference between painful and non-painful conditioning ( p = 0.31). Neither was there any difference between genders ( p = 0.28); mean male VAS scores were 91 ± 21% and mean female scores were 89 ± 27% during (vs. before) conditioning. Conclusion Electrically induced muscle pain was not inhibited by a painful heat stimulus to the forearm. The reduction in muscle pain may be results of habituation. The lack of a DNIC effect may have been caused by the relatively small skin area receiving the conditioning stimulus, and excludes a conclusion on gender effects.

Objective The objective of this study was to test if offset analgesia could be evoked using a noncontact thermal stimulator. Offset analgesia [J. Neurophysiol. 87:2205–2208, 2002] is defined as an unproportionally large decrease in pain intensity following a slight decrease in stimulation intensity. The importance of differences in thermal properties between human hairy and glabrous skin was investigated. Methods A 20W diode laser (970 nm) was used for the thermal stimulation. A fast (50 images/s) infrared camera measured the skin temperature and a temperature controlled feedback control loop adjusted the laser power. 8 subjects participated in this study. Stimulations were applied on the dorsum side and in the palm of the hand. Subjects were instructed to continuously rate the pain intensity. First the subject was stimulated using both a rising 35–45 °C staircase and a decreasing 45–35 °C staircase in both skin types; each staircase step was 1 °C and lasted for 15 s. Offset analgesia was tested by stimulating the hairy skin on the dorsum of the hand using two sequential temperature plateaus (48–48 °C, 48–49 °C, 49–48 °C and 49–49 °C). Each plateau was held for 5 s. Results For the staircase stimulations identical surface temperatures were perceived significantly higher in glabrous than in hairy skin ( p < 0.001). The offset analgesia test showed that a decrease in temperature from 49 to 48 °C evoked a drop in the pain rating which was significantly lower than observed during a 48–48 °C stimulation ( p < 0.001) indicating offset analgesia. Conclusion A non-contact thermal stimulator is able to evoke offset analgesia. Furthermore, it was noted that a high penetration laser causes higher pain ratings in glabrous skin than in hairy skin—a relationship which is opposite to low penetration lasers (CO 2 laser) and contact heat stimulation.

Postsurgical inflammation leads to sensitisation of “sleeping” nociceptors, which enhance pain perception and induce hyperalgesia. Prostaglandin E2 plays a central role in this process. Synovial microdialysis technique allows analyses of biological markers of local inflammation simultaneous with a close follow up of the patient’s pain experience. Tissue injury (or surgery) initiates liberation of inflammatory mediators and hyperalgesic substances. This project is translational and aims at exploring the relationship between perceived acute postoperative pain and inflammation. Microdialysis of synovial tissue and pain score after arthroscopy is of special interest to study since the natural pain course and the local inflammation can be observed in patients with no analgesic therapy. Methods This is a clinical observational study of local inflammatory mediators and perceived pain in patients undergoing knee arthroscopy in general anesthesia with propofol, remifentanil and fentanyl. Microdialysis of the synovial membrane was performed in all patients every 20 min for 140 min postoperatively (seven samples). At the same intervals PGE2 was measured and correlated with patients report of pain intensity on a 0–100mm visual analogue scale (VAS). Results Five patients (1 female, 4 male) who did not receive any non-steroidal antiinflammatory drugs or paracetamol were included. The pain intensity was 1–34mmVAS and the PGE2 levels were from 293 pg/ml to 5818 pg/ml. Maximum pain score (mean 23 and SD 12mm VAS) and PGE2 levels (mean 2026 pg/ml and SD 1380 pg/ml) occurred about 40 min after surgery. Correlation analysis shows a significant correlation ( R = 0.48, p = 0.004). Conclusion This pilot study indicates a positive correlation between postoperatively perceived pain and local PGE2 concentration.

Introduction A previously healthy 19-year-old woman, who had symptoms of gastric-oesophagela reflux disease for over one year, was transferred to our specialist hospital three weeks post fundoplication operation at a local hospital. She had several episodes with severe retrosternal pain lasting minutes to hours which was stabbing in character. She persistently experienced what was thought to be episodes of oesophageal spasm associated with food intake or movement. She required gradually escalating doses of opioids, both transdermal, intramuscular and intravenous. She was started on a regime of transdermal opioids in addition to iv opioids for the acute pain episodes. This was later supplemented with a PCA pump. Despite the increase in pain and in CRP, the patient was continued on an opioid reduction regime initiated by the surgeons six weeks post surgery. Two months post fundoplication she developed respiratory failure. Discussion The patient had a prolonged and painful postoperative period after an elective fundoplication. Her retrosternal pain had lasted over a year prior to surgery, but postoperatively a spasmic pain escalated substantially leaving her hospitalised. The symptoms where initially thought to be due to oesophageal spasm, but gastroscopy was normal and manometry showed normal contraction pressures in the oesophagus. It was discovered that she had right sided pleuritis that had developed into an empyema. She was intubated, sedated and initially treated with two chest drains before undergoing a right sided thoracotomy that removed the remaining pleural fluid areas and the postinfectious tissue. The exact mechanism of this complication is not known. Conclusion Oesophageal spasms after fundoplication is a known complication in about 1 in 1000 patients and is associated with intense spasmic retrosternal pain. However, empyema also needs to be considered where postoperative pain persists. It is an extremely rare and painful complication.

Background The prevalence of persistent postoperative pain in the general population is poorly documented, but clinical studies indicate that the problem is common. Aim The aim of this study was (1) to assess the prevalence of persistent postoperative pain among individuals operated during the last 3 years in a general population and (2) to describe factors associated with chronic postoperative pain. Materials and methods As part of a cross-sectional health survey in the municipality of Tromsø, North Norway, all participants answered questions on surgery, persisting pain and sensory abnormalities in the area of surgery. N = 12,984. Age 30–87 years, median 59. 53.4% women. Pain intensity was reported using a 0–10 Numeric Rating Scale (0–10 NRS). Logistic regression was used to reveal any associations between pain and self-reported hyposensitivity, hypersensitivity and allodynia. Results 2316 individuals (17.8%) had surgery between 3 months and 3 years prior to the survey. 826 (40.4%)of the 2044 who answered a questionnaire on postsurgical pain, reported having some degree of pain in the area of surgery. Of these 826 individuals, 45.2% had pain, when at worst, of moderate or severe intensity, i.e. 0–10 NRS of 4 or higher. The areas of surgery carrying the strongest association with persistent pain were (in descending order of frequency): (1) Shoulder/ upper arm [74.5% (108/145)], (2) back [73.9% (65/88)], (3) lungs [66.7% (8/12)], (4) knee/lower leg [63.7% (179/281)], (5) hand [58.8% (90/153)]. (6) hip/thigh [58.3% (74/127)] and (7) ankle/foot [58.7% (84/143)]. 18.3% (413) had reduced sensitivity in the area near the surgical scar, while 10.6% (240) reported hypersensitivity and 5.6% (127) allodynia. For those reporting hypoesthesia, the odds ratio (OR) for having pain was 2.71 (95% confidence interval 2.08–3.53), for those reporting hyperesthesia, OR was 4.82 (3.24–7.18) and for those with allodynia 5.83 (3.12–10.90). Conclusions 3 months or more after surgery, nearly half of the respondents report having pain in the area of surgery. In this survey, there is a strong association between persistent pain and the presence of both hyposensitivity, hypersensitivity and allodynia.

Background Economy is an important part of chronic pain. Aim To describe the economy in chronic non-malignant pain patients attending a 13-week Rehabilitation Program (RP). Methods All patients participating in the RP 2006–2008 were evaluated at baseline (BL) and at follow-up (FU) after an observation period of mean … month in relation to: (1) work-income (WI) or (2) transfer income (TI), comprised by: (a) sick-leave (SL), (b) sick pension (SP), (c) social benefit (SB) and (d) rehabilitation benefit (RB). The economic impact on state and county and the time to age pension was calculated. Results 117 patients attended the RP. At BL 23 patients had WI and 19 maintained this at FU (3 were on SP and 1 on RB). 90 patients were on TI at BL: 58 on SL at BL changed to 20 on SP + 23 on WI + 6 on SB + 1 on RB + 6 maintained SL, 12 on SB at BL changed to 6 on WI+ 1 on SP + 5 still on SB. 7 on RB at BL changed to 6 on WI + 1 on RB. The economic situation was concluded for 97 patients (83%). State expenses were increased by 540,000 Euro and county savings was 698,000 Euro. The societal savings were 158,000 Euro. The total costs for the RP was 421,000 Euro. Costs balanced savings after 2.7 years. The average time to age pension for the participating patients was 25 years. The potential accumulated savings thus amounted to 3.5 million Euros. Conclusions The 13-week Rehabilitation Program was highly cost effective: expenses for the program balanced savings after 3 years and the time to age pension for the participating patients was 25 years. The potential accumulated saving per patient was 30,000 Euro.

Introduction We have developed somatocognitive therapy as a hybrid of Mensendieck physiotherapy and cognitive psychotherapy. Womenwith chronic pelvic pain (CPP) and vulvodynia (chronic pain of the vulvae and vestibulum, VD) were recruited into two separate treatment protocols as described. Methods 60 patients with CPP were recruited from the Department of Gynaecology at the Oslo University Hospital into a randomized, controlled intervention study. The patients were randomized into three treatment groups, receiving (1) treatment as usual, (2) somatocognitive therapy, and (3) in addition receiving cognitive therapy. The patients were assessed by means of SMT, Visual Analogue Score of Pain (VAS), and General Health Questionnaire (GHQ-30) at baseline, after three months of out-patient therapy and at 1 year follow-up. 9 women with VD were treated in an outpatient setting by physiotherapy students under senior supervision, each receiving in all 16 therapy sessions over 8 weeks, and scored for motor patterns (SMT) and pain (VAS) before and after therapy. Results In the control group, no significant change was found. In the group receiving somatocognitive therapy, significant reduction in pain score and improvement in motor function were found the end of therapy, and the significant improvement continued through the follow-up period. GHQ scores were significantly improved for the scores representing level of anxiety and coping, and improved for depression. In the group receiving cognitive therapy in addition, the VAS scores were reduced to the same level as the group receiving only somatocognitive therapy, whereas the motor patterns showed slightly less improvement than for those women that did not receive cognitive intervention. In the women with VD somatocognitive therapy resulted in significantly reduction in pain scores (by an average of 66%), and significant improvement of motor patterns, especially for the scores for gait (56%) and respiration (88%). Conclusions Somatocognitive therapy is a new approach that appears to be very promising in the management of chronic gynaecological pain. Short-term out-patient treatment significantly reduces pain scores and improves motor function, especially with respect to respiration, gait and movement (ability to relax). The approach is now being used in a randomized, controlled intervention study including patient with chronic low back, neck and shoulder, and widespread pain.

Objectives In recent years, pigs are used increasingly for biomedical translational research and often considered superior to rodent models. However, only very few pain assays for quantification of behavioural nociceptive responses are available for pigs. This experiment is part of a larger project aiming at developing pain assays for pigs, and the present aim was to examine behavioural responses towards mechanical cutaneous stimulation applied to the caudal part of the metatarsus on the hind legs of pigs using an IITC Electronic von Frey Anesthesiometer. Methods Nine slaughter pigs (bodyweight 54 ± 0.7 kg) were subjected to handheld nociceptive mechanical stimulation using the electronic von Frey anesthesiometer (max 1000 g). The animals were kept in one group and tested while slightly fixated in a testroom, to which they had been habituated. Each nociceptive test consisted of 4 single stimulations. Results The animals responded behaviourally after single stimulations of 12–1000 g (8% censored) and had a mean threshold for leg movements of 540 ± 85 g. Neither the type of behavioural responses (four categories from slight leg movements to kicking) nor the mechanical threshold was affected by successive stimulations (517 ± 126, 413 ± 84, 598 ± 97 and 499 ± 122 g, for first to fourth stimulation, respectively) or differed between right and left leg (522 ± 86 g vs. 492 ± 64 g, respectively). No correlations between mechanical thresholds and behavioural responses were found. Conclusion The results show that pigs respond behaviourally to mechanical von Frey stimulation directed at the hind legs, and suggest that responses were not affected by successive stimulations.