Postoperative hypoesthesia and pain: qualitative assessment after open and laparoscopic inguinal hernia repair

BACKGROUND: Chronic pain is an important outcome variable after inguinal hernia repair that is generally not assessed by objective methods. The aim of this study was to objectively investigate chronic pain and hypoesthesia after inguinal hernia repair using three types of operation: open suture, open mesh, and laparoscopic. METHODS: A total of 96 patients were included in the study with a median follow-up of 4.7 years. Open suture repair was performed in 40 patients (group A), open mesh repair in 20 patients (group B), and laparoscopic repair in 36 patients (group C). Hypoesthesia and pain were assessed using von Frey monofilaments. Quality of life was investigated with Short Form 36. RESULTS: Pain occurring at least once a week was found in 7 (17.5%) patients of group A, in 5 (25%) patients of group B, and in 6 (16.6%) patients of group C. Area and intensity of hyposensibility were increased significantly after open nonmesh and mesh repair compared to those after laparoscopy (p = 0.01). Hyposensibility in patients who had laparoscopic hernia repair was significantly associated with postoperative pain (p = 0.03). Type of postoperative pain was somatic in 19 (61%), neuropathic in 9 (29%), and visceral in 3 (10%) patients without significant differences between the three groups. CONCLUSIONS: The incidence of hypoesthesia in patients who had laparoscopic hernia repair is significantly lower than in those who had open hernia repair. Hypoesthesia after laparoscopic but not after open repair is significantly associated with postoperative pain. Von Frey monofilaments are important tools for the assessment of inguinal hypoesthesia and pain in patients who had inguinal hernia repair allowing quantitative and qualitative comparison between various surgical techniques.

[Neither Descartes nor Freud? current pain models in psychosomatic medicine]

Models explaining chronic pain based on the mere presence or absence of peripheral somatic findings or which view pain of psychological origin when there is no somatic explanation, have their shortcomings. Current scientific knowledge calls for distinct pain concepts, which integrate neurobiological and neuropsychological aspects of pain processing.

The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain

The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressed cannabinoid receptor 2 (CB2). It is found in relatively high concentrations in many spices and food plants. A number of studies have shown that CB2 is critically involved in the modulation of inflammatory and neuropathic pain responses. In this study, we have investigated the analgesic effects of BCP in animal models of inflammatory and neuropathic pain. We demonstrate that orally administered BCP reduced inflammatory (late phase) pain responses in the formalin test in a CB2 receptor-dependent manner, while it had no effect on acute (early phase) responses. In a neuropathic pain model the chronic oral administration of BCP attenuated thermal hyperalgesia and mechanical allodynia, and reduced spinal neuroinflammation. Importantly, we found no signs of tolerance to the anti-hyperalgesic effects of BCP after prolonged treatment. Oral BCP was more effective than the subcutaneously injected synthetic CB2 agonist JWH-133. Thus, the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions.

p.L1612P, a Novel Voltage-gated Sodium Channel Nav1.7 Mutation Inducing a Cold Sensitive Paroxysmal Extreme Pain Disorder

BACKGROUND Mutations in the SCN9A gene cause chronic pain and pain insensitivity syndromes. We aimed to study clinical, genetic, and electrophysiological features of paroxysmal extreme pain disorder (PEPD) caused by a novel SCN9A mutation. METHODS Description of a 4-generation family suffering from PEPD with clinical, genetic and electrophysiological studies including patch clamp experiments assessing response to drug and temperature. RESULTS The family was clinically comparable to those reported previously with the exception of a favorable effect of cold exposure and a lack of drug efficacy including with carbamazepine, a proposed treatment for PEPD. A novel p.L1612P mutation in the Nav1.7 voltage-gated sodium channel was found in the four affected family members tested. Electrophysiologically the mutation substantially depolarized the steady-state inactivation curve (V1/2 from -61.8 ± 4.5 mV to -30.9 ± 2.2 mV, n = 4 and 7, P < 0.001), significantly increased ramp current (from 1.8% to 3.4%, n = 10 and 12) and shortened recovery from inactivation (from 7.2 ± 5.6 ms to 2.2 ± 1.5 ms, n = 11 and 10). However, there was no persistent current. Cold exposure reduced peak current and prolonged recovery from inactivation in wild-type and mutated channels. Amitriptyline only slightly corrected the steady-state inactivation shift of the mutated channel, which is consistent with the lack of clinical benefit. CONCLUSIONS The novel p.L1612P Nav1.7 mutation expands the PEPD spectrum with a unique combination of clinical symptoms and electrophysiological properties. Symptoms are partially responsive to temperature but not to drug therapy. In vitro trials of sodium channel blockers or temperature dependence might help predict treatment efficacy in PEPD.

Reliability of Quantitative Sensory Tests in a Low Back Pain Population.

BACKGROUND AND OBJECTIVES Reliability is an essential condition for using quantitative sensory tests (QSTs) in research and clinical practice, but information on reliability in patients with chronic pain is sparse. The aim of this study was to evaluate the reliability of different QST in patients with chronic low back pain. METHODS Eighty-nine patients with chronic low back pain participated in 2 identical experimental sessions, separated by at least 7 days. The following parameters were recorded: pressure pain detection and tolerance thresholds at the toe, electrical pain thresholds to single and repeated stimulation, heat pain detection and tolerance thresholds at the arm and leg, cold pain detection threshold at the arm and leg, and conditioned pain modulation using the cold pressor test.Reliability was analyzed using the coefficient of variation, the coefficient of repeatability, and the intraclass correlation coefficient. It was judged as acceptable or not based primarily on the analysis of the coefficient of repeatability. RESULTS The reliability of most tests was acceptable. Exceptions were cold pain detection thresholds at the leg and arm. CONCLUSIONS Most QST measurements have acceptable reliability in patients with chronic low back pain.

Expectations and effects of a single yoga session on pain perception

BACKGROUND Several studies show yoga may benefit chronic pain management. We investigated the effect of a single yoga session on the perception of pain, measured by a standardized pain provocation test in healthy yoga participants while also comparing pain perception to participants' own expectations. MATERIALS AND METHODS Ninety yoga participants were recruited at hatha yoga schools in Switzerland. Pain perception was measured with a standardized algometric pain provocation test; i.e., a calibrated peg was applied for 10 seconds after which the participant rated pain intensity on a 0-10 numerical rating scale. The test was applied to the middle finger, ear lobe, and second toe before and after a 60-minute yoga session. RESULTS Sixty out of 90 (66.7%) yoga participants expected a reduced pain perception after the yoga session. However, 36 (40%) participants actually experienced less pain after compared to before the yoga session. But overall, pain perception statistically did not significantly change from before to after the yoga session at any of the three body locations assessed. The expectations and also the previous yoga experience did not significantly influence the participants' pain perception. CONCLUSIONS Regardless of the high positive expectations on the influence of yoga on pain, a single yoga session does not significantly influence pain perception induced by a pain provocation test. Hypoalgesic effects of yoga should be explained otherwise.

In vivo assessment of HCN channel current (I(h)) in human motor axons

The "Trond" protocol of nerve excitability tests has been used widely to assess axonal function in peripheral nerve. In this study, the routine Trond protocol was expanded to refine assessment of cAMP-dependent, hyperpolarization-activated current (I(h)) activity. I(h) activity is generated by hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels in response to hyperpolarization. It limits activity-dependent hyperpolarization, contributes to neuronal automaticity, and is implicated in chronic pain states. Published data regarding I(h) activity in motor nerve are scant. We used additional strong, prolonged hyperpolarizing conditioning stimuli in the threshold electrotonus component of the Trond protocol to demonstrate the time-course of activation of I(h) in motor axons. Fifteen healthy volunteers were tested on four occasions during 1 week. I(h) action was revealed in the threshold electrotonus by the limiting and often reversal, after about 100 ms, of the threshold increase caused by strong hyperpolarizing currents. Statistical analysis by repeated-measures analysis of variance enabled confidence limits to be established for variation between subjects and within subjects. The results demonstrate that, of all the excitability parameters, those dependent on I(h) were the most characteristic of an individual, because variance between subjects was more than four times the variance within subjects. This study demonstrates a reliable method for in vivo assessment of I(h,) and also serves to document the normal variability in nerve excitability properties within subjects.

Expression of the nociceptin precursor and nociceptin receptor is modulated in cancer and septic patients

A role of nociceptin and its receptor (NOP) in pain and immune function has been suggested. The hypothesis was that mRNA expression of NOP and the nociceptin precursor pre-pronociceptin (pN/OFQ) in peripheral blood cells differs in end-stage cancer patients suffering from chronic pain and septic intensive care unit (ICU) patients compared with healthy controls.

Prospective randomized trial comparing sutured with sutureless mesh fixation for Lichtenstein hernia repair: long-term results

Following Lichtenstein hernia repair, up to 25% of patients experience prolonged postoperative and chronic pain as well as discomfort in the groin. One of the underlying causes of these complaints are the compression or irritation of nerves by the sutures used to fixate the mesh. We compared the level and rate of chronic pain in patients operated with the classical Lichtenstein technique fixated by sutures to patients with sutureless mesh fixation technique.

Transcutaneous electrostimulation for osteoarthritis of the knee

BACKGROUND: Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in the elderly. Transcutaneous electrical nerve stimulation (TENS), interferential current stimulation and pulsed electrostimulation are used widely to control both acute and chronic pain arising from several conditions, but some policy makers regard efficacy evidence as insufficient. OBJECTIVES: To compare transcutaneous electrostimulation with sham or no specific intervention in terms of effects on pain and withdrawals due to adverse events in patients with knee osteoarthritis. SEARCH STRATEGY: We updated the search in CENTRAL, MEDLINE, EMBASE, CINAHL and PEDro up to 5 August 2008, checked conference proceedings and reference lists, and contacted authors. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared transcutaneously applied electrostimulation with a sham intervention or no intervention in patients with osteoarthritis of the knee. DATA COLLECTION AND ANALYSIS: We extracted data using standardised forms and contacted investigators to obtain missing outcome information. Main outcomes were pain and withdrawals or dropouts due to adverse events. We calculated standardised mean differences (SMDs) for pain and relative risks for safety outcomes and used inverse-variance random-effects meta-analysis. The analysis of pain was based on predicted estimates from meta-regression using the standard error as explanatory variable. MAIN RESULTS: In this update we identified 14 additional trials resulting in the inclusion of 18 small trials in 813 patients. Eleven trials used TENS, four interferential current stimulation, one both TENS and interferential current stimulation, and two pulsed electrostimulation. The methodological quality and the quality of reporting was poor and a high degree of heterogeneity among the trials (I(2) = 80%) was revealed. The funnel plot for pain was asymmetrical (P < 0.001). The predicted SMD of pain intensity in trials as large as the largest trial was -0.07 (95% CI -0.46 to 0.32), corresponding to a difference in pain scores between electrostimulation and control of 0.2 cm on a 10 cm visual analogue scale. There was little evidence that SMDs differed on the type of electrostimulation (P = 0.94). The relative risk of being withdrawn or dropping out due to adverse events was 0.97 (95% CI 0.2 to 6.0). AUTHORS' CONCLUSIONS: In this update, we could not confirm that transcutaneous electrostimulation is effective for pain relief. The current systematic review is inconclusive, hampered by the inclusion of only small trials of questionable quality. Appropriately designed trials of adequate power are warranted.

Differences in endplate deformation of the adjacent and augmented vertebra following cement augmentation

Vertebral cement augmentation can restore the stiffness and strength of a fractured vertebra and relieve chronic pain. Previous finite element analysis, biomechanical tests and clinical studies have indirectly associated new adjacent vertebral fractures following augmentation to altered loading. The aim of this repeated measures in situ biomechanical study was to determine the changes in the adjacent and augmented endplate deformation following cement augmentation of human cadaveric functional spine units (FSU) using micro-computed tomography (micro-CT). The surrounding soft tissue and posterior elements of 22 cadaveric human FSU were removed. FSU were assigned to two groups, control (n = 8) (loaded on day 1 and day 2) and augmented (n = 14) (loaded on day 1, augmented 20% cement fill, and loaded on day 2). The augmented group was further subdivided into a prophylactic augmentation group (n = 9), and vertebrae which spontaneously fractured during loading on day 1 (n = 5). The FSU were axially loaded (200, 1,000, 1,500-2,000 N) within a custom made radiolucent, saline filled loading device. At each loading step, FSUs were scanned using the micro-CT. Endplate heights were determined using custom software. No significant increase in endplate deformation following cement augmentation was noted for the adjacent endplate (P > 0.05). The deformation of the augmented endplate was significantly reduced following cement augmentation for both the prophylactic and fracture group (P < 0.05, P < 0.01, respectively). Endplate deformation of the controls showed no statistically significant differences between loading on day 1 and day 2. A linear relationship was noted between the applied compressive load and endplate deflection (R (2) = 0.58). Evidence of significant endplate deformation differences between unaugmented and augmented FSU, while evident for the augmented endplate, was not present for the adjacent endplate. This non-invasive micro-CT method may also be useful to investigate endplate failure, and parameters that predict vertebral failure.

Discovery of novel CB2 receptor ligands by a pharmacophore-based virtual screening workflow

Cannabinoid receptor 2 (CB(2) receptor) ligands are potential candidates for the therapy of chronic pain, inflammatory disorders, atherosclerosis, and osteoporosis. We describe the development of pharmacophore models for CB(2) receptor ligands, as well as a pharmacophore-based virtual screening workflow, which resulted in 14 hits for experimental follow-up. Seven compounds were identified with K(i) values below 25 microM. The CB(2) receptor-selective pyridine tetrahydrocannabinol analogue 8 (K(i) = 1.78 microM) was identified as a CB(2) partial agonist. Acetamides 12 (K(i) = 1.35 microM) and 18 (K(i) = 2.1 microM) represent new scaffolds for CB(2) receptor-selective antagonists and inverse agonists, respectively. Overall, our pharmacophore-based workflow yielded three novel scaffolds for the chemical development of CB(2) receptor ligands.

The influence of a continuous rate infusion of dexmedetomidine on the nociceptive withdrawal reflex and temporal summation during isoflurane anaesthesia in dogs

Objective To examine the influence of a low dose dexmedetomidine infusion on the nociceptive withdrawal reflex and temporal summation in dogs during isoflurane anaesthesia. Study design Prospective experimental blinded cross-over study. Animals Eight healthy mixed breed dogs, body weight Mean +/- SD 26.5 +/- 8.4 kg and age 25 +/- 16 months. Methods Anaesthesia was induced with propofol and maintained with isoflurane (Fe'ISO 1.3%) delivered in oxygen and air. After stabilization, baseline recordings (time 0) were obtained, then a dexmedetomidine bolus (1 mug kg(-1) IV) followed by a continuous rate infusion (1 mug kg(-1) hour(-1) ) or saline placebo were administered. At times 10, 30 and 60 minutes after the initial bolus, electrical stimulations of increasing intensity were applied over the lateral plantar digital nerve, and administered both as single and as repeated stimuli. The resulting reflex responses were recorded using electromyography. Data were analysed using a multivariable linear regression model and a Kruskal Wallis test for single stimulation data, and repeated measures anova and paired t-test for repeated stimulation data. Results The AUC for the stimulus-response curves after single stimulation were similar for both treatments at time 0. At times 10, 30 and 60 the AUCs for the stimulus-response curves were significantly lower with dexmedetomidine treatment than with placebo. Temporal summation was evident in both treatments at times 0, 10, 30 and 60 starting from a stimulation intensity of 10 mA. The magnitude of temporal summation was smaller in dexmedetomidine than in placebo treated dogs at time 10, 30 and 60, but not at time 0. Conclusions During isoflurane anaesthesia, low dose dexmedetomidine suppresses the nociceptive reflex responses after single and repeated electrical stimulation. Clinical relevance This experimental study confirms previous reports on its peri-operative efficacy under clinical conditions, and further indicates that dexmedetomidine might reduce the risk of post-operative chronic pain development.

Acute effects of stochastic resonance whole body vibration

AIM: To investigate the acute effects of stochastic resonance whole body vibration (SR-WBV) training to identify possible explanations for preventive effects against musculoskeletal disorders. METHODS: Twenty-three healthy, female students participated in this quasi-experimental pilot study. Acute physiological and psychological effects of SR-WBV training were examined using electromyography of descending trapezius (TD) muscle, heart rate variability (HRV), different skin parameters (temperature, redness and blood flow) and self-report questionnaires. All subjects conducted a sham SR-WBV training at a low intensity (2 Hz with noise level 0) and a verum SR-WBV training at a higher intensity (6 Hz with noise level 4). They were tested before, during and after the training. Conclusions were drawn on the basis of analysis of variance. RESULTS: Twenty-three healthy, female students participated in this study (age = 22.4 ± 2.1 years; body mass index = 21.6 ± 2.2 kg/m2). Muscular activity of the TD and energy expenditure rose during verum SR-WBV compared to baseline and sham SR-WBV (all P < 0.05). Muscular relaxation after verum SR-WBV was higher than at baseline and after sham SR-WBV (all P < 0.05). During verum SR-WBV the levels of HRV were similar to those observed during sham SR-WBV. The same applies for most of the skin characteristics, while microcirculation of the skin of the middle back was higher during verum compared to sham SR-WBV (P < 0.001). Skin redness showed significant changes over the three measurement points only in the middle back area (P = 0.022). There was a significant rise from baseline to verum SR-WBV (0.86 ± 0.25 perfusion units; P = 0.008). The self-reported chronic pain grade indicators of pain, stiffness, well-being, and muscle relaxation showed a mixed pattern across conditions. Muscle and joint stiffness (P = 0.018) and muscular relaxation did significantly change from baseline to different conditions of SR-WBV (P < 0.001). Moreover, muscle relaxation after verum SR-WBV was higher than after sham SR-WBV (P < 0.05). CONCLUSION: Verum SR-WBV stimulated musculoskeletal activity in young healthy individuals while cardiovascular activation was low. Training of musculoskeletal capacity and immediate increase in musculoskeletal relaxation are potential mediators of pain reduction in preventive trials.

Hormonal Contraceptive Use and the Prevalence of Endometriotic Lesions at Different Regions within the Peritoneal Cavity.

Endometriosis is an estrogen-dependent disease that can lead to chronic pain and subfertility. Endometriotic lesions found in different locations are heterogeneous and may represent a collection of related but distinct conditions. Whether there is a relationship between hormonal contraceptive (HC) use and endometriosis is still controversial. The purpose of this study was to determine whether HC use affected the prevalence of endometriotic lesions differently based on lesion location. Data was retrospectively collected from 161 patients presenting to the Berne University Women's Hospital between 2008 and 2012 for laparoscopic investigation. Women with histologically proven endometriosis were included in the study and patients were grouped according to lesion location and HC use. The results of the study indicate that HC users are significantly less likely to have endometriotic lesions on the ovaries, although in contrast, no difference was observed in the incidence of lesions in the rectovaginal septum (RVS) or peritoneal region. In addition, women using HC who were diagnosed with endometriotic lesions on the peritoneum were significantly younger than women with lesions in other locations. In conclusion, women with endometriosis who are currently using HC are less likely to have ovarian endometriotic lesions than in alternate locations.