Pain Threshold Tolerance Research Articles

Association between preoperative magnetic resonance imaging, pain intensity and quantitative sensory testing in patients awaiting lumbar diskectomy

Magnetic resonance imaging (MRI) offers important information regarding the morphology, location and size of a herniated disc, which influences the decision to offer lumbar diskectomy (LD). This study aims to examine the association between clinical neurophysiologic indices including pain intensity and quantitative sensory testing (QST), and the degree of lumbar nerve root compromise depicted on magnetic resonance (MR) in patients awaiting LD. With institutional ethical approval, 16 patients (American Society of Anaesthesiologists Grades I-II, 18-65 years) with radicular pain for greater than 3 months undergoing elective LD were studied. Preoperative pain was assessed using (i) a visual analogue scale measuring pain intensity at rest and with movement and (ii) by quantifying pain sensory thresholds (St), pain perception thresholds (PPt), and pain tolerance threshold (PTt) using QST. MR images were independently graded by two radiologists blinded to the clinical data using the Pfirrmann grading system. Statistical analyses using Student's t-tests and Pearson's correlation were preformed where appropriate. This study showed that: (i) findings on MR imaging corresponded with the symptomatic side and distribution of the pain; (ii) the degree of nerve root compromise, detected on MRI correlated with increased pain intensity at rest; and (iii) QST identified a trend towards higher St, PPt and PTt in patients with higher Pfirrmann grades. The Pfirrmann grading system of nerve root compromise may be clinically useful preoperatively as a method of identifying individuals who would benefit most from LD. However, additional studies with greater patient numbers and longer follow-up are required to definitively confirm the findings of this study.

Pain sensitivity and experimentally induced sensitisation in red haired females

Introduction and aim Pain sensitivity has been linked to the melanocortin-1 receptor (MC1R) gene. A mutation in MC1R can result in pale skin and red hair in humans and may modulate pain responses in general. Human studies have shown that women with non-functional MC1R's were sensitive to experimental induced cold and heat pain. A study demonstrated that females with red hair required higher dose of anesthesia than females with dark hair to experience analgesia to electrical stimulation. Moreover, women expressing non-functional MC1Rs display greater analgesia from opioid analgesia. If redheads in general respond differently to pain and analgesics, this is of clinical importance. The aim of this study was therefore to investigate pain sensitivity and experimentally induced sensitisation in red haired females. Method Twenty healthy females with pale skin and red hair (mean age 32 years, range 20–55) and 20 healthy females with blond/dark hair (mean age 31 years, range 20–51) participated in this study. The pain tolerance thresholds to heat and pressure stimulation were determined. Hyperalgesia was induced experimentally by applying 0.075% topical capsaicin cream for 30 min. The secondary pin-prick hyperalgesic area was estimated with a calibrated filament (von Frey hair, 15 g) and the area of allodynia by a soft brush. This was done 0, 30, 60, and 90 min after cream removal. Results Neither heat nor pressure pain tolerance thresholds were changed in the two groups. The secondary pin-prick hyperalgesic areas were significantly smaller for red haired females than blond/dark haired females ( P = 0.014). There were no significant differences in the allodynic areas. Discussion As the secondary hyperalgesic response evoked by topical capsaicin is a central phenomenon, the observed smaller pin-prick hyperalgesic area in the red haired females could indicate a central role of MCRs in development or maintenance of hyperalgesia. Central involvement of MC1Rs or dysfunction of peripheral MC1Rs activating central MC4Rs has been suggested to influence pain sensitivity. The difference observed between red haired and non-red haired females may have implications for pain management regimens as compounds interacting with sensitisation such as NMDA-antagonists or alpha-2-delta-ligands may exert different types of action in people with MC1R mutation. Conclusion The present study showed that red haired females were less sensitive to topical capsaicin induced pin-prick hyperalgesia compared with blond/dark haired females. Implications The smaller hyperalgesic area in redheads could be a manifestation of central anti-hyperalgesic involvement of MCRs and could have an influence on the treatment of pain as well as in studies investigating anti-hyperalgesic drugs.

Increased Sympathetic Activity in Chronic Pancreatitis Patients Is Associated With Hyperalgesia

ABSTRACTPain treatment in chronic pancreatitis patients is difficult, with pain frequently relapsing or persisting. Recent studies suggest that altered central nervous system pain processing underlies the chronic pain state in these patients. There is evidence that increased sympathetic activity may also play a role in some chronic pain syndromes. This study assessed sympathetic nervous system activity and its relation to pain processing in patients with severe painful chronic pancreatitis. The authors postulated that chronic pancreatitis patients with more sympathetic activity exhibit more generalized hyperalgesia. In 16 chronic pancreatitis patients, sympathetic activity was measured via venous plasma norepinephrine (NE) levels (supine, standing). Pain processing was quantified via pressure pain tolerance thresholds (PPTs) in dermatomes T10 (pancreatic area), C5, T4, L1. Five patients showed increased supine plasma NE levels (NE ≥ 3.0 nmol/L). PPTs were lower in patients with increased NE levels (INE) compared with patients with normal NE (NNE) (means [95% confidence interval]: INE 402 kPa [286–517] versus NNE 522 kPa [444–600]; P = .042). In severe chronic pancreatitis patients, increased sympathetic activity and hyperalgesia appear associated, suggesting that sympathetic activity may also play a role in these patients’ pain.

Correlation of preoperative pain threshold and pain tolerance threshold with the intensity of stress reaction induced by endotracheal intubation and skin incision

Objective To investigate the correlation of preoperative pain threshold and pain tolerance threshold with the intensity of stress reaction induced by endotracheal intubation and skin incision. Methods Fifty ASA Ⅰ or Ⅱ women, aged 20-55 yr, undergoing elective abdominal surgery requiring at least a 10-cm-long skin incision under general anesthesia, were studied. The electricity dolorimeter was used to measure the patients＇ pain sensitivity, including pain threshold and pain tolerance, and a State Trait Anxiety Inventory （STAI） was also used to examine the mental state the day before surgery. Total intravenous anesthesia was performed in all the patients.Anesthesia was induced with TCI of propofol 4 μg/ml （effect-site concentration）. After patients lost consciousness,fentanyl 3 μg/kg and vecuronium 0.1 mg/kg were injected intravenously. Tracheal intubation was performed 3 min later and the patients were mechanically ventilated. MAP and HR were recorded and arterial blood samples were taken for determinvress reaction induced by endotracheal intubation and skin incision, but there is no correlation between pain threshold and the intensity of stress reaction. Key words: Pain threshold; Stress; Intubation,intratracheal

Reference values of mechanical and thermal pain tests in a pain-free population

Quantitative sensory tests are widely used in human research to evaluate the effect of analgesics and explore altered pain mechanisms, such as central sensitization. In order to apply these tests in clinical practice, knowledge of reference values is essential. The aim of this study was to determine the reference values of pain thresholds for mechanical and thermal stimuli, as well as withdrawal time for the cold pressor test in 300 pain-free subjects. Pain detection and pain tolerance thresholds to pressure, heat and cold were determined at three body sites: (1) lower back, (2) suprascapular region and (3) second toe (for pressure) or the lateral aspect of the leg (for heat and cold). The influences of gender, age, height, weight, body-mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short-Form 36 (SF-36) were analyzed by multiple regressions. Quantile regressions were performed to define the 5th, 10th and 25th percentiles as reference values for pain hypersensitivity and the 75th, 90th and 95th percentiles as reference values for pain hyposensitivity. Gender, age and/or the interaction of age with gender were the only variables that consistently affected the pain measures. Women were more pain sensitive than men. However, the influence of gender decreased with increasing age. In conclusion, normative values of parameters related to pressure, heat and cold pain stimuli were determined. Reference values have to be stratified by body region, gender and age. The determination of these reference values will now allow the clinical application of the tests for detecting abnormal pain reactions in individual patients.

Pain Perception Studies in Tension-Type Headache

Tension-type headache (TTH) is a disorder with high prevalence and significant impact on society. Understanding of pathophysiology of TTH is paramount for development of effective treatments and prevention of chronification of TTH. Our aim was to review the findings from pain perception studies of pathophysiology of TTH as well as to review the research of pathophysiology of TTH. Pain perception studies such as measurement of muscle tenderness, pain detection thresholds, pain tolerance thresholds, pain response to suprathreshold stimulation, temporal summation and diffuse noxious inhibitory control (DNIC) have played a central role in elucidating the pathophysiology of TTH. It has been demonstrated that continuous nociceptive input from peripheral myofascial structures may induce central sensitization and thereby chronification of the headache. Measurements of pain tolerance thresholds and suprathreshold stimulation have shown presence of generalized hyperalgesia in chronic tension-type headache (CTTH) patients, while DNIC function has been shown to be reduced in CTTH. One imaging study showed loss of gray matter structures involved in pain processing in CTTH patients. Future studies should aim to integrate pain perception and imaging to confirm this finding. Pharmacological studies have shown that drugs like tricyclic anti-depressant amitriptyline and nitric oxide synthase inhibitors can reverse central sensitization and the chronicity of headache. Finally, low frequency electrical stimulation has been shown to rapidly reverse central sensitization and may be a new modality in treatment of CTTH and other chronic pain disorders.

Severity of Acute Pain After Breast Surgery Is Associated With the Likelihood of Subsequently Developing Persistent Pain

Persistent postsurgical pain (PPSP) after surgery for breast cancer has a prevalence of 20% to 52%. Neuroplastic changes may play a role in the aetiology of this pain. The principal objective of this study was to examine the relationship between acute pain after surgery for breast cancer and the likelihood of subsequently developing PPSP. Twenty-eight women undergoing surgery for breast cancer completed visual analogue scales for pain and anxiety, the McGill Pain Questionnaire (long form) and the Hospital Anxiety and Depression Scale. Analgesic requirements and adverse effects of analgesic therapy were noted. Quantitative sensory testing was carried out perioperatively using an electrical stimulus, and the sensation perception, pain perception, and pain tolerance thresholds were measured bilaterally at the T4 dermatomes and at the contralateral L5 dermatome. Patients with and without PPSP 3 months postoperatively were compared in terms of these parameters. Eight participants (28.6%) reported PPSP. Those who subsequently developed PPSP reported greater pain scores on the McGill Pain Questionnaire 5 days postoperatively than those that did not (pain rating index, P=0.014; present pain intensity, P=0.032). None had sought medical attention for their persistent pain. Patients with and without PPSP were similar in terms of mental status (anxiety and depression), analgesic consumption, adverse effects of analgesic therapy, and changes on QST. Patients who developed PPSP experienced pain of greater intensity on the fifth postoperative day than those that did not.

The antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes

The aim of this study was to search for a possible association between the variant allele of the single nucleotide polymorphisms A118G in the OPRM1 gene and C3435T and G2677T/A in the ABCB1 gene and altered antinociceptive effect and adverse drug reactions of oxycodone. Thirty-three healthy subjects exposed to experimental pain including electrical stimulation and the cold pressor test were included. A118G: We found that the variant G allele was associated with reduced antinociceptive effect as measured by pain tolerance thresholds to single electrical nerve stimulation (8% increase vs. 25% for the wild-type carriers, P = 0.007). C3435T: The carriers of the variant T allele generally had less adverse drug reactions on oxycodone than the carriers of the wild-type genotype. G2677T/A: The carriers of the variant T allele had a better antinociceptive effect of oxycodone than the carriers of the wild-type genotype in the cold pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25% reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug reactions. The combined wild-type genotype 3435CC-2677GG was associated with less antinociceptive effect of oxycodone in the discomfort rating of the cold pressor test (13% reduction vs. 23%, P = 0.019) and more severe adverse drug reactions than the carriers of the variant alleles. We found a moderate association between less antinociceptive effect of oxycodone and the variant allele of A118G. There was strong association between less adverse drug reactions of oxycodone and the variant alleles of C3435T and G2677T/A.

Analysis of thermal pain sensitivity and psychological profiles in different subgroups of TMD patients

This study evaluated differences in pain sensitivities and psychological profiles among different temporomandibular disorder (TMD) pain subtypes. Evaluation was done on 36 normal subjects and 39 TMD patients with high Graded Chronic Pain scale scores. TMD patients were placed in three pain subgroups (myogenous, arthrogenous, mixed) using the Research Diagnostic Criteria for TMD (RDC/TMD) axis I guidelines. RDC/TMD axis II profiles including depression and somatization were analysed. Cold pain threshold (CPT), heat pain threshold (HPT), and heat pain tolerance threshold (HPTT) were measured on three facial regions (anterior temporalis, masseter, TMJ) and a leg region (anterior tibialis). The arthrogenous pain subgroup showed significantly higher CPT and lower HPT and HPTT in the facial region, and lower HPTT in the anterior tibialis region compared with normal and myogenous pain subgroups. The myogenous pain subgroup had significantly higher somatization scores than normal and arthrogenous pain subgroups, and higher depression scores than normal subjects. The results suggest that peripheral and/or central sensitization are present in chronic arthrogenous pain more so than in myogenous pain, and this phenomenon appears to take place regardless of the patient's psychological profiles. These results may explain the underlying mechanism that aggravates TMD pain.

The effects of gabapentin in human experimental pain models

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.

Changes in pain tolerance thresholds with administration of an analgesic anti-inflammatory agent and anti-anxiety agent

Changes in pain tolerance thresholds with administration of an analgesic anti-inflammatory agent and anti-anxiety agent

Patients with Chronic Pain After Abdominal Surgery Show Less Preoperative Endogenous Pain Inhibition and More Postoperative Hyperalgesia: A Pilot Study

ABSTRACTChronic pain is common and undesirable after surgery. Progression from acute to chronic pain involves altered pain processing. The authors studied relationships between presence of chronic pain versus preoperative descending pain control (diffuse noxious inhibitory controls; DNICs) and postoperative persistence and spread of skin and deep tissue hyperalgesia (change in electric/pressure pain tolerance thresholds; ePTT/pPTT) up to 6 months postoperatively. In 20 patients undergoing elective major abdominal surgery under standardized anesthesia, we determined ePTT/pPTT (close to [abdomen] and distant from [leg] incision), eDNIC/pDNIC (change in ePTT/pPTT with cold pressor pain task; only preoperatively), and a 100 mm long pain visual analogue scale (VAS) (0 mm = no pain, 100 mm = worst pain imaginable), both at rest and on movement preoperatively, and 1 day and 1, 3, and 6 months postoperatively. Patients reporting chronic pain 6 months postoperatively had more abdominal and leg skin hyperalgesia over the postoperative period. More inhibitory preoperative eDNIC was associated with less late postoperative pain, without affecting skin hyperalgesia. More inhibitory pDNIC was linked to less postoperative leg deep tissue hyperalgesia, without affecting pain VAS. This pilot study for the first time links chronic pain after surgery, poorer preoperative inhibitory pain modulation (DNIC), and greater postoperative degree, persistence, and spread of hyperalgesia. If confirmed, these results support the potential clinical utility of perioperative pain processing testing.

The Role of Central Hypersensitivity in the Determination of Intradiscal Mechanical Hyperalgesia in Discogenic Pain

The primary aim of the present study was to investigate whether there is a relationship between central hypersensitivity (assessed by pressure pain thresholds of uninjured tissues) and intradiscal pain threshold during discography. The secondary aim was to test the hypothesis that peripheral noxious stimulation dynamically modulates central hypersensitivity. Twenty-four patients with positive provocation discography were tested for central hypersensitivity by pressure algometry before and after the intervention with assessments of pressure pain detection and tolerance thresholds. Intradiscal pain threshold was assessed by measuring intradiscal pressure at the moment of pain provocation during discography. Correlation analyses between intradiscal pain threshold and pressure algometry were made. For the secondary aim, pressure algometry data before and after discography were compared. Significant correlation with intradiscal pain threshold was found for pressure pain detection threshold at the toe (regression coefficient: 0.03, P = 0.05) and pressure pain tolerance thresholds at the nonpainful point at the back (0.02, P = 0.024). Tolerance threshold at the toe was a significant predictor for intradiscal pain threshold only in multiple linear regression (0.036, P = 0.027). Detection as well as tolerance thresholds significantly decreased after discography at the painful and the nonpainful point at the back, but not at the toe. Central hypersensitivity may influence intradiscal pain threshold, but with a modest quantitative impact. The diagnostic value of provocation discography is therefore not substantially impaired. Regional, but not generalized central hypersensitivity is dynamically modulated by ongoing peripheral nociceptive input.

Episodic and chronic migraineurs are hypersensitive to thermal stimuli between migraine attacks

To determine if migraineurs have evidence of interictal cutaneous sensitisation. Thermal and mechanical pain thresholds in 20 episodic migraineurs, 20 chronic migraineurs, and 20 non-migraine control subjects were compared. Quantitative sensory testing was conducted when subjects had been migraine-free for at least 48 h. Heat, cold and mechanical pain thresholds, and heat and cold pain tolerance thresholds were measured. Thermal pain thresholds and thermal pain tolerance thresholds differed significantly by headache group (P = 0.001). During the interictal period, episodic and chronic migraineurs were more sensitive to thermal stimulation than non-migraine controls. Interictal sensitisation may predispose the migraineur to development of headaches, may be a marker of migraine activity, and a target for treatment.

Perioperative Pregabalin Improves Pain and Functional Outcomes 3 Months After Lumbar Discectomy

Patient outcome after lumbar discectomy for radicular low back pain is variable and the benefit is inconsistent. Many patients continue to experience pain 3 months after surgery. Pregabalin, a membrane stabilizer, may decrease perioperative central sensitization and subsequent persistent pain. Forty patients undergoing lumbar discectomy were randomly allocated to receive either pregabalin (300 mg at 90 minutes preoperatively and 150 mg at 12 and 24 hours postoperatively) or placebo at corresponding times in a double-blinded manner. Our primary outcome was the change in the present pain intensity (PPI) (visual analog scale [VAS], 0-100 mm [PPI-VAS, McGill Pain Questionnaire]) from preoperatively to 3 months postoperatively. The decrease in PPI-VAS score at 3 months was greater in patients who received pregabalin (37.6 +/- 19.6 mm) (mean +/- sd) than those who received placebo (25.3 +/- 21.9 mm) (P = 0.08). The Roland Morris disability score at 3 months was less in patients who received pregabalin (2.7 +/- 2.4) than in those who received placebo (5.6 +/- 4.8) (P = 0.032). Pregabalin administration was associated with greater pain tolerance thresholds in both lower limbs compared with placebo at 24 hours postoperatively. Perioperative pregabalin administration is associated with less pain intensity and improved functional outcomes 3 months after lumbar discectomy.

Pain: Putting the Whole Person at the Centre

In the current climate of patient-centred or client-centred care, it is increasingly important to recognize the unique personal experience of pain. As physical therapy students in the 1970s, the authors frequently wondered why the amount of pain experienced in response to a specific injury did not appear to be uniform among patients. Why did some patients have more post-op pain than others? Why did each person behave so differently in response to pain and injury? Why did some patients develop chronic pain after a shoulder injury or become disabled by back pain, whereas others did not, even though they appeared to have a similar injury? At that time there was no “physiological explanation” for the differences in individual outcomes. In fact, we now know that one of the common misconceptions among health care professionals was that the intensity and quality of pain experienced by each person should directly reflect the type and extent of tissue injury.1 This mistaken belief often led clinicians to dichotomize the mind/body experience of pain, so that the clinical approach focused on isolating and treating tissue injury, with little effort to consider the person experiencing the pain. Individual differences in the pain experience and in observed pain behaviours were often considered—consciously or unconsciously—to be “in the patient's head.” Thankfully, pain research has grown exponentially in the last 30 years, and we now understand that pain actually is “in the brain” and that differences in each person's pain experience reflect the individual's unique nervous-system processing, based on a complex integration of genetic,2,3 biopsychomotor,4–6 and social/environmental factors. For example, recent genetic research has identified individual differences in pain tolerance and pain threshold.7 In addition, with the advent of central nervous system imaging, the roles of so-called non-physiological factors in pain processing have actually been visualized in the form of brain activity.

Acupuntura de compensación (balance): un estudio experimental sobre su eficacia en el tratamiento de los dolores radiculares en un modelo de rata con hernia discal

Background Lumbar disc herniation (LDH) is a common clinical disease accounting for lumbocrural pain in the majority of the patients. The incidence of LDH has risen quickly in the past years. The theory of balance acupuncture is a new method firstly established by Dr. Wang Wenyuan and further developed according to a large amount of clinical studies which have come to emphasize its immediate therapeutic effects. Swiftness of effect as well as an easy point selection and handling are among the advantages of this technique. Objectives By applying balance acupuncture in a clinical setting, we have obtained data reporting a significant effect on LDH. However, the mechanisms are still unknown. The clinical symptoms of radicular pain are mainly induced by pathological changes due to mechanical compression and the chemical inflammation process. With this theoretical background, we used a rat lumbar disc herniation model with radiculopathy which resembled the pathological situation of radicular pain in LDH of humans. We observed the beneficial effect of balance acupuncture on LDH with radiculopathy and tried to decipher its working mechanism for clinical treatments. Methods Male SD (Sprague-Dawley) rats were randomly and evenly assigned to a blank group, a sham-operation group, a model group and a treatment group, respectively. In the model group, radiculopathy of LDH was simulated by cerclaging the L5 nerve root, followed by a detection of the change of claw-latency after thermally stimulated withdrawal. Moreover, the histological changes were judged by haematoxylin-eosin (HE) staining, whereby the physiological marker IL-1β was detected, showing stimulation by the balance acupoints “lumbago” and “hip pain”. Results 1) Radiculopathy caused by LDH-nerve compression can cause hyperalgesia of the lower limbs, reduction of the pain tolerance threshold, edema of the nerve root tissue, disappearance of the axon, and infiltration of inflammatory cells. 2) Radiculopathy caused by LDH can cause an increase of IL-1β. There was a positive correlation between IL-1β and the inflammatory response of the nerve root as well as the amount of pain. 3) Balance acupuncture can diminish fiber edema of the nerve root and demyelination, reduce the responses of the inflammation and stress, and promote healing of the injured nerve root. Conclusion Balance acupuncture can regulate the responses to the hyperalgesia in radiculopathy caused by LDH. It can influence the expression level of some cytokines, and eventually repair the disordered functions of the nerve root to some extent, all of which might be regulated through neuroendocrinal-immune system related cascades and pathways. Therefore, balance acupuncture is a novel method for treatment of disease like LDH with radicular pain, which is worthy to be tested extensively in clinical surroundings.

Association of human μ‐opioid receptor gene polymorphism A118G with fentanyl analgesia consumption in Chinese gynaecological patients

One hundred and seventy-four Chinese gynaecology patients were studied for the impact of A118G polymorphism in the micro-opioid receptor gene (OPRM1) on pain sensitivity and postoperative fentanyl consumption. Pre-operatively, the pain threshold and pain tolerance threshold were measured using electrical stimulation. A118G polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Intravenous fentanyl patient-controlled analgesia provided postoperative pain management, assessed using a visual analogue scale and fentanyl consumed in the first 24 h after surgery was noted. We found the prevalence of G118 allele was 31.3%. The A118G polymorphism had a gene-dose-dependent effect on electrical pain tolerance threshold. Fentanyl consumption was also significantly different in patients with different OPRM1 genotypes (homozygotes for 118G consumed more than did heterozygotes or homozygotes for 118A). Fentanyl consumption increased in accordance with the number of 118G alleles. We conclude that OPRM1 gene analysis may help predict individual opioid sensitivity and so optimise postoperative pain control.

Analgesic Efficacy of Peripheral κ-Opioid Receptor Agonist CR665 Compared to Oxycodone in a Multi-modal, Multi-tissue Experimental Human Pain Model

Peripherally selective opioids may be beneficial in visceral pain management due to absence of centrally mediated side effects. The objectives of this study were: (1) to assess the effects of a peripherally selective tetrapeptide kappa-opioid receptor agonist, CR665, on experimental pain from multi-modal stimulation of skin, muscle, and viscera, and (2) contrast these effects with those of oxycodone (centrally acting opioid). The study was designed as a single-center, single-dose, randomized, double-blind, placebo and active-controlled, double-dummy, three-way, crossover study in healthy males. Subjects received the following treatments in randomized order: (1) CR665 (0.36 mg/kg) administered intravenously over 1 h, (2) oxycodone (15 mg) administered orally, and (3) placebo administered intravenously and orally. The following pain tests were used: (1) cutaneous pinch pain tolerance threshold, (2) pressure pain detection and tolerance thresholds, (3) cuff pressure pain tolerance threshold, and (4) pain rating thresholds to distension and thermal stimulation of the esophagus. Measurements were performed before dosing and at 30, 60, and 90 min after dosing. Compared to placebo, oxycodone elevated cutaneous pinch pain tolerance (P < 0.001) and cuff pressure pain tolerance threshold (P < 0.001), as well as pain rating thresholds (visual analogue scale = 7) to esophageal distension (P < 0.001) and thermal stimulation (P < 0.002). Compared to placebo, CR665 significantly increased the pain rating threshold to esophageal distension (P < 0.005) but reduced the pain tolerance threshold to skin pinching (P = 0.007). CR665 had a selective effect on visceral pain. Oxycodone exhibited a generalized effect, elevating thresholds for cutaneous, deep somatic, and visceral pain stimulation.

Lowering of Sensory, Motor, and Pain-Tolerance Thresholds With Burst Duration Using Kilohertz-Frequency Alternating Current Electric Stimulation: Part II

Ward AR, Lee Hung Chuen WL. Lowering of sensory, motor, and pain-tolerance thresholds with burst duration using kilohertz-frequency alternating current electric stimulation: part II. Objective To determine the optimum burst duration for discrimination between sensory, motor, and pain tolerance thresholds using 20-Hz bursts of kilohertz-frequency sinusoidal alternating current (AC) applied transcutaneously to human participants. Design A within-subject, repeated-measures trial. Setting A research laboratory. Participants Healthy young adults (N=20). Interventions Bursts of AC electric stimulation at frequencies of 1 and 4kHz. The burst frequency was 20Hz. Burst durations ranged from 250 microseconds (for 1 cycle of 4-kHz AC) and 1 millisecond (for 1 cycle of 1-kHz AC) to 50 milliseconds (continuous AC). Main Outcome Measures Measurement of sensory, motor, and pain-tolerance thresholds. Results Thresholds decreased to a minimum with increasing burst duration. The minimum threshold identified the utilization time over which summation of subthreshold stimuli occurs. Utilization times were different for sensory (∼20ms), motor (∼30ms), and pain (>50ms) and were much higher than found in a previous study that used a higher burst frequency (50Hz). As with the previous study, relative thresholds were found to vary with burst duration. Despite the very different utilization times, maximum separation between sensory, motor, and pain thresholds was found to occur with bursts in the range of 1 to 4 milliseconds, the same range found in the previous study. Conclusions Our conclusions concur with those reported previously and support the contention that short-duration kilohertz-frequency AC bursts (1–4ms) have a more useful role in rehabilitation than the long-duration kilohertz-frequency bursts that characterize Russian and interferential currents.