Electrical Detection Thresholds Research Articles

Peripheral vs. central determinants of vibrotactile adaptation.

Long-lasting mechanical vibrations applied to the skin induce a reversible decrease in the perception of vibration at the stimulated skin site. This phenomenon of vibrotactile adaptation has been studied extensively, yet there is still no clear consensus on the mechanisms leading to vibrotactile adaptation. In particular, the respective contributions of 1) changes affecting mechanical skin impedance, 2) peripheral processes, and 3) central processes are largely unknown. Here we used direct electrical stimulation of nerve fibers to bypass mechanical transduction processes and thereby explore the possible contribution of central vs. peripheral processes to vibrotactile adaptation. Three experiments were conducted. In the first, adaptation was induced with mechanical vibration of the fingertip (51- or 251-Hz vibration delivered for 8 min, at 40× detection threshold). In the second, we attempted to induce adaptation with transcutaneous electrical stimulation of the median nerve (51- or 251-Hz constant-current pulses delivered for 8 min, at 1.5× detection threshold). Vibrotactile detection thresholds were measured before and after adaptation. Mechanical stimulation induced a clear increase of vibrotactile detection thresholds. In contrast, thresholds were unaffected by electrical stimulation. In the third experiment, we assessed the effect of mechanical adaptation on the detection thresholds to transcutaneous electrical nerve stimuli, measured before and after adaptation. Electrical detection thresholds were unaffected by the mechanical adaptation. Taken together, our results suggest that vibrotactile adaptation is predominantly the consequence of peripheral mechanoreceptor processes and/or changes in biomechanical properties of the skin.

Quantitative sensory testing of dentinal sensitivity in healthy humans

Objective The study was to provide information on quantitative sensory testing (QST) of normal teeth to establish a sensory profile and investigate the possible gender and regional differences. Materials and methods A modified QST protocol was applied on both left and right upper-jaw incisors and pre-molar sof 14 healthy men and 14 age-matched healthy women (18–25 years). Mechanical stimulus sensitivity (MSS), cold detection threshold (CDT), cold pain threshold (CPT), warm detection threshold (WDT), heat pain threshold (HPT), electrical detection threshold (EDT) and electrical pain threshold (EPT) were determined from the four teeth (labial side of incisor and buccal side of the first premolar). The QST parameters were analysed by ANOVA. Results The applied mechanical or thermal stimuli did not evoke any pain sensation. A normal tooth did not seem to be able to distinguish between the warm or cold stimuli applied. No significant differences were found between genders (p > 0.099) or teeth (p > 0.053) regarding mechanical and thermal stimuli. The EDT and EPT were significantly higher in the pre-molar compared with incisor (p < 0.002) without gender differences (p > 0.573). Conclusion: The established methods and results provided important information on diagnosis and treatment evaluation of dentinal hypersensitivity.

Effects of sleep deprivation on pain sensitivity in healthy subjects

Introduction The relationship between sleep and pain has recently been seen as reciprocal. Pain may disturb sleep, but changes in sleep pattern could also influence pain perception. The aim of this study was to investigate the effects of partial sleep deprivation (PSD) on electrical pain sensitivity in healthy adults. Materials and methods Twenty healthy male subjects with good sleep quality (age 20–39 years) were investigated twice, once after habitual sleep (HS) and once after partial sleep deprivation. Overnight polysomnographic recordings were done during the night of HS, and actigraphic recordings were done during the night of PSD (2 h of time-in-bed at dawn). Electrical pain detection thresholds and tolerance thresholds were measured in the morning after each night. Subjective pain intensity during repetitive electrical pain stimulation was measured with visual analogue scale, and sleepiness was measured with Stanford sleepiness scale. All subjects completed daily sleep and pain diaries during the experimental period. Results Total sleep time of HS and PSD nights were 449 i3/4 20.6 min and 96.1 i3/4 12.3 min. Compared to HS, PSD decreased significantly electrical pain detection threshold (28.5 i3/4 4.5 mA vs. 23.6 i3/4 5.4 mA, p p p p Conclusion These findings suggest that reduced sleep time is associated with increased pain sensitivity, and there is an interaction between sleep and the brain mechanism of pain perception.

Altered central pain processing after pancreatic surgery for chronic pancreatitis

Chronic abdominal pain is common in chronic pancreatitis (CP) and may involve altered central pain processing. This study evaluated the relationship between pain processing and pain outcome after pancreatic duct decompression and/or pancreatic resection in patients with CP. Patients with CP underwent quantitative sensory testing. Pain processing was measured via electrical pain detection (ePDT) and electrical pain tolerance (ePTT) thresholds in dermatomes C5 and L4. Inhibitory descending pain control mechanisms were assessed using the conditioned pain modulation (CPM) paradigm. Healthy controls and patients with CP were compared, and patients with CP and a poor pain outcome (visual analogue scale (VAS) score greater than 30) were compared with those with a good pain outcome (VAS score 30 or less). Forty-eight patients with CP had lower ePDT, ePTT and CPM responses compared with values in 15 healthy controls (P < 0·030). The sum of ePDT values was lower in patients with a poor pain outcome than in those with a good outcome (median 7·1 versus 11·2 mA; P = 0·008). There was a correlation with the VAS score and the sum of ePDT values (rs = -0·45, P = 0·016) and ePTT values (rs = -0·46, P = 0·011), and CPM response (rs = -0·43, P = 0·006) in patients with CP. After pain-relieving pancreatic surgery, patients with CP exhibit altered central pain processing compared with that in healthy controls. Poor pain outcomes are associated with more central sensitization and more pronociceptive descending pain modulation, and this should be considered when managing persistent pain after pain-relieving surgery for CP.

P 7. Effects of transcutaneous spinal direct current stimulation (tsDCS) on long-term potentiation (LTP)-like central sensitization of pain sensation

Strong stimulation of nociceptive afferents results in hyperalgesia based on facilitation of spinal nociceptive pathways, which plays a role in pathological pain conditions. This central sensitization can be experimentally induced via nociceptive high frequency stimulation (HFS) at high intensities in animals (nociceptive LTP) and humans (pain-LTP), and has many mechanistic and molecular similarities with LTP described in the hippocampus. Since LTP in the hippocampus can be inhibited by post-synaptic hyperpolarization, altering the resting membrane potential (RMP) of neurons in the spinal cord could also modulate pain sensitivity and experimentally-induced hyperalgesia. Transcranial direct current stimulation over M1 is thought to enhance or reduce motor neuron excitability via an NMDA-dependent mechanism in a polarity-specific manner. When applied over the spine (tsDCS) this technique may have a similar effect on the spinal circuitry and has in fact already been shown to affect motor and nociceptive reflex responses. We therefore postulated that tsDCS could alter the hyperalgesia induced by nociceptive HFS in a polarity-specific manner. In a double-blind, randomized study 14 healthy right-handed male volunteers each took part in three sessions separated by at least 2 weeks. Painful electrical trains of HFS (5 trains of 100 Hz for 1 s, 9 s onset interval) were given to the right distal thigh. TsDCS was applied directly following HFS via two 7 × 5 cm saline-soaked sponges over T12 vertebral process and the left shoulder. Anodal, cathodal (2.5 mA, 15 min) and sham (1.5 mA, 45 s) stimulation polarities referred to the electrode over T12. Sensory perception was tested on both sides using electrical and mechanical stimuli before (baseline) and at three time points (0, 30, 60 min) post-tsDCS. Subjects gave pain ratings from 0 (non pain) to 100 (worst pain imaginable), resulting in electrical detection threshold (EDT), mechanical pain threshold (MPT), and electrical and mechanical pain sensitivity (EPS and MPS) scores. Baseline and post-stimulation scores were compared using repeated measures ANOVA and Tukey HSD post hoc tests to identify time and stimulation effects. HFS induced significant hyperalgesia after not only sham tsDCS but also following anodal and cathodal polarities. MPS and EPS pain ratings were significantly elevated for all three post-stimulationtime points in all sessions ( p < 0.001–0.03). EDT was significantly reduced at T0 in all sessions ( p < 0.03) whereas MPT decreased marginally, which never reached significance at any time point in any session. None of the responses differed significantly between tsDCS and sham condition. This study confirmed that LTP-like central sensitization induced by HFS is a robust effect and for the first time showed that tsDCS applied immediately following HFS does not influence the resulting hyperalgesia seen within the first hour. Whether sensitized neurons are more resistant to the applied current or whether RMP changes from tsDCS occur in neurons insignificant to the development of hyperalgesia is unknown. To test this first hypothesis we plan to repeat this study, this time applying tsDCS before HFS.

Ranking of parameters of pain hypersensitivity according to their discriminative ability in chronic low back pain

Low back pain is associated with plasticity changes and central hypersensitivity in a subset of patients. We performed a case-control study to explore the discriminative ability of different quantitative sensory tests in distinguishing between 40 cases with chronic low back pain and 300 pain-free controls, and to rank these tests according to the extent of their association with chronic pain. Gender, age, height, weight, body mass index, and psychological measures were recorded as potential confounders. We used 26 quantitative sensory tests, including different modalities of pressure, heat, cold, and electrical stimulation. As measures of discrimination, we estimated receiver operating characteristics (ROC) and likelihood ratios. Six tests seemed useful (in order of their discriminative ability): (1) pressure pain detection threshold at the site of most severe pain (fitted area under the ROC, 0.87), (2) single electrical stimulation pain detection threshold (0.87), (3) single electrical stimulation reflex threshold (0.83), (4) pressure pain tolerance threshold at the site of most severe pain (0.81), (5) pressure pain detection threshold at suprascapular region (0.80), and (6) temporal summation pain threshold (0.80). Pressure and electrical pain modalities seemed most promising and may be used for diagnosis of pain hypersensitivity and potentially for identifying individuals at risk of developing chronic low back pain over time.

Evaluation of Neurosensory Changes in the Infraorbital Nerve following Zygomatic Fractures

To evaluate the incidence and recovery of persistent sensory disturbances of the infraorbital (IO) nerve after isolated zygomatic complex fractures with various treatment methods. The study was inclusive of isolated unilateral zygomatic complex fractures and fractures of IO rim .Tests performed were Pin prick and Electrical detection threshold test. The evaluation was done preoperatively, after 1month and after 6months of surgery. The results suggested that neurosensory disturbance was present in all the patients with zygomatic complex fractures. At 1month post-operatively some sensory deficit was present in all the patients on the affected side. After 6months all the patients showed near to normal improvement comparable to normal side. Study shows that earlier the surgical intervention, more the recovery of the nerve injury is appreciable during the 1 and 6 months follow up period.

Increased β-Endorphin Levels and Generalized Decreased Pain Thresholds in Patients With Limited Jaw Opening and Movement-Evoked Pain From the Temporomandibular Joint

Patients with limited jaw opening and movement-evoked pain from the temporomandibular joint have moderate to severe pain that may be relieved by surgery. The purpose of this study was to investigate if the preoperative state is associated with alterations in plasma β-endorphin (βE) levels and pain thresholds. Eighteen female patients with painful unilateral temporomandibular joint and 18 age-matched healthy women participated. After blood sampling for analysis of plasma βE levels, pressure pain thresholds over the masseter muscles and index fingers were recorded with an electronic algometer. Electrical detection and pain thresholds were recorded with the PainMatcher (Cefar Medical AB, Lund, Sweden) device. Nonparametric statistics, ie, Mann-Whitney U test and Spearman correlation test, was used for statistical analyses. The patients showed higher plasma βE levels (P = .013) and lower pressure pain thresholds over the masseter muscle at the painful side (P = .041) and bilaterally over the index fingers compared with the controls (P < .05 for all comparisons). High plasma βE levels correlated to increased electrical detection thresholds (n = 36, r = 0.347, P = .038). This study showed that patients with limited jaw opening and movement-evoked pain from the temporomandibular joint had significantly higher plasma βE levels and lower pressure pain thresholds in the orofacial area and at remote sites compared with pain-free, healthy, age-matched controls. An increased level of βE seems insufficient to inhibit pain and central sensitization. Further studies are warranted to elucidate the relation between βE and pain thresholds secondary to stress, inflammation, and discectomy.

Prolonged gingival cold allodynia: a novel finding in patients with atypical odontalgia

The aim of this study was to examine atypical odontalgia (AO) patients with extraoral quantitative sensory testing (EQST) and an intraoral mucosal cold test. Twenty-one subjects with AO and 18 control subjects underwent EQST for electrical and thermal pain and detection thresholds. Cold was applied to painful mucosal areas in AO patients and randomly in control subjects. Electrical pain thresholds were higher in AO patients than in control subjects in the same dermatome affected by the pain (P = .03), but no significant differences were observed in electrical detection thresholds and heat pain and detection thresholds at other sites. Cold application was painful in control and AO subjects, but duration of pain sensation was significantly longer in AO patients (P = .019 in contralateral side; P = .029 in affected side). The finding of extended painful aftersensation following cold application in AO patients supports the involvement of central mechanisms. The cold test is clinically easy to apply and of clinically significant value.

A randomised controlled study examining the short-term effects of Strain–Counterstrain treatment on quantitative sensory measures at digitally tender points in the low back

Strain–Counterstrain (SCS) intervention has been claimed to elicit immediate and sustained reductions in tenderness at digitally tender points (DTPs), however, there is little experimental evidence to support this. Twenty-eight volunteer participants with low back pain – LBP (17 females and 11 males with mean [SD] age of 39.2 [11.1] and Oswestry disability index of 15.7 [8.6]) participated in this controlled, within-participants study of the immediate and short-term effects of SCS intervention, on pressure pain threshold (PPT) electrical detection threshold (EDT) and electrical pain threshold (EPT) at DTPs in the low back region. Immediate increases in PPT at DTPs were found following all interventions; control intervention: 30.7 kPa [CI 95% – 3.3–64.8] ( p = 0.041), sham-SCS intervention: 48.2 kPa [CI 95% 14.8–81.7] ( p = 0.008) and SCS intervention: 93.4 kPa [CI 95% 60.0–126.9] ( p < 0.0001). Results suggest that SCS intervention does elicit an immediate quantifiable reduction in tenderness at DTPs but that some of this reduction is attributable to the manual-contact component of the treatment. Increases in PPT at DTPs following SCS intervention did not appear to be maintained between 24 and 96 h after treatment. A further finding was that the control intervention elicited significant increases in both EDT ( p = 0.044) and EPT ( p = 0.026). The explanation for these findings is unclear.

Sensory characteristics of tender points in the lower back

Palpation of tender points in superficial tissue is commonly undertaken in the management of musculoskeletal pain. The sensory characteristics of digitally tender points (DTPs) have not been defined. This study had two major aims: 1) to characterise ‘Strain–Counterstrain’ DTPs, using quantitative sensory testing (QST) in participants with low back pain (LBP); 2) to compare corresponding points at lumbar sites in participants with LBP to those without LBP. Fifteen participants with LBP (9 females), mean (SD) Oswestry scores 20.8 (10.1)) and 15 participants without LBP (6 females) were included. QST was undertaken by a single examiner blind to the location of DTPs and included measurement of electrical detection and electrical pain threshold, thermal (hot/cold) detection and thermal pain threshold, vibration detection threshold and pressure-pain threshold. In participants with LBP, DTPs demonstrated significantly lower electrical detection and electrical pain thresholds compared to contralateral non-tender points (p < 0.0001). These findings may be indicative of altered central processing of Aβ afferents with terminal receptors at DTPs. Participants with LBP demonstrated elevated cold pain thresholds at lower back sites and at the peripheral shoulder site compared to participants without LBP (p < 0.001). This may also indicate augmented central pain processing in participants with LBP.

The role of IL-6 and IL-1β in painful perineural inflammatory neuritis

Inflammation along a nerve trunk (perineural inflammation), without detectable axonal damage, has been shown to induce transient pain in the organ supplied by the nerve. The aims of the present study were to study the role IL-6 and IL-1β, in pain induced by perineural inflammation. Methods IL-6 and IL-1β secretion from rat’s sciatic nerves, L-5 Dorsal Root Ganglia (DRG), and the hind paw skin, 3 and 8 days following exposure of the nerve to Complete Freund’s Adjuvant (CFA), were measured using ELISA method. Hind paw tactile-allodynia, mechano-hyperalgesia, heat-allodynia and electrical detection thresholds were tested up to 8 days following the application of CFA, IL-6 or IL-1β adjacent to the sciatic nerve trunk. Employing electrophysiological recording, saphenous nerve spontaneous activity, nerve trunk mechano-sensitivity and paw tactile detection threshold (determined by recording action potential induced by the lowest mechanical stimulus) were assessed 3 and 8 days following exposure of the nerve trunk to CFA, IL-6, or IL-1β. Results IL-6 and IL-1β secretion from the nerve was significantly elevated on the 3rd day post-operation (DPO). On the 8th DPO, IL-6 levels returned to baseline while IL-1β levels remained significantly elevated. The DRG cytokine’s level was increased on the 3rd and 8th DPOs, contralateral cytokine’s level was increased on the 3rd DPO. The skin IL-6 level was increased bilaterally on the 3rd DPO and returned to baseline on the 8th DPO. IL-1β levels increased in the affected side on the 3rd and bilaterally on the 8th DPO. Direct application of IL-6 or CFA on the sciatic nerve induced significant hind paw tactile-allodynia from the 1st to 5th DPOs, reduced electrical detection threshold from the 1st to 3rd DPOs, mechano-hyperalgesia from 3rd to 5th DPOs and heat-allodynia on the 3rd DPO. Direct application of IL-1β induced paw tactile and heat-allodynia on the 7–8th DPOs and mechano-hyperalgesia on the 5–8th DPOs. Perineural inflammation significantly increased spontaneous activity myelinated fibres 3 and 8 days following the application. Direct application of IL-6 induced elevation of spontaneous activity on the 3rd while IL-1β on the 8th DPO. Nerve mechano-sensitivity was significantly increased on the 3rd day following exposure to CFA and IL-6 and on the 8th following CFA application. The rat’s paw lowest mechanical force necessary for induction of action potential, was significantly reduced 3 days following CFA application. Conclusion IL-6 and IL-1β play an important role in pain induced by perineural inflammation. IL-6 activity is more prominent immediately following application (2–5th DPOs), while IL-1β, activity is more significant in a later stage (5–8th DPOs).

Can Preoperative Electrical Nociceptive Stimulation Predict Acute Pain After Groin Herniotomy?

Preoperative identification of patients at risk for high-intensity postoperative pain may be used to predict patients at risk for development of a persistent pain state and allocate patients to more intensive specific pain therapy. Preoperative pain threshold to electrocutaneus stimulation has recently been shown to correlate to acute postoperative pain after cesarean section, but the findings have not been confirmed in larger studies or other procedures. Preoperative electrical pain detection threshold and pain tolerance were assessed in patients undergoing a primary unilateral groin hernia repair. The correlation between the pain data for electrical stimulation was compared with the postoperative pain during the first week in 165 patients, whereof 3 were excluded. Preoperative electrical pain detection threshold and electrical pain tolerance threshold did not correlate to postoperative pain (rho = -0.13, P = .09, and rho = -1.2, P = .4, respectively. Although preoperative electrical nociceptive stimulation may predict patients at risk of high-intensity acute pain after other surgical procedures, this was not the case in groin hernia repair patients receiving concomitant treatment with acetaminophen and ibuprofen.

Mental nerve neuropathy: patient characteristics and neurosensory changes

The objective of this study was to analyze the etiological factors and neurosensory signatures of patients attending with a primary complaint of numb chin. Charts of 27 patients referred to Hadassah School of Dental Medicine, Jerusalem, Israel, with a complaint of unilateral numbness or paresthesias of the chin were reviewed. Demographic and etiologic data and special tests, including imaging, that were prescribed as necessary for the treatment protocol were evaluated. The neurosensory evaluation protocol included assessment of detection thresholds to electrical stimulation (assessing large myelinated nerve fibers) and heat (assessing thin unmyelinated nerve fibers) in the mental and infraorbital nerves regions bilaterally. Data from 8 healthy, age and sex-matched subjects who underwent similar sensory testing served as the control group. Invasive dental procedures (eg, extractions, implants) were the etiologic factor in 63% of the cases. Inflammatory pathoses (15%) (eg, periapical periodontitis or infection), and malignant lesions (22%) were identified as causative in the remaining patients. Frank nerve injury due to advanced malignant processes was characterized by significantly elevated heat and electrical thresholds (hyposensitivity). Inflammatory process was accompanied by reduced electrical detection thresholds (hypersensitivity). This study concurs with previous studies that sensory hyposensitivity accompanies nerve damage. Accordingly, quantitative sensory testing may contribute to the diagnostic process of patients with mental nerve neuropathy. In this sample of patients, the most common cause for mental nerve neuropathy was dental treatment followed by malignant metastasis.

Effects of deafening and cochlear implantation procedures on postimplantation psychophysical electrical detection thresholds

Previous studies have shown large decreases in cochlear implant psychophysical detection thresholds during the weeks following the onset of electrical testing. The current study sought to determine the variables underlying these threshold decreases by examining the effects of four deafening and implantation procedures on detection thresholds and implant impedances. Thirty-two guinea pigs were divided into four matched groups. Group I was deafened and implanted Day 0 and began electrical testing Day 1. Group II was deafened and implanted Day 0 and began electrical testing Day 45. Group III was deafened Day 0, implanted Day 45 and began electrical testing Day 46. Group IV was not predeafened but was implanted Day 0 and began electrical testing Day 1. All groups showed threshold decreases over time but the magnitude of change, time course and final stable threshold levels depended on the type and time course of treatment. Impedances increased over the first two weeks following the onset of electrical testing except in Group II. Results suggest that multiple mechanisms underlie the observed threshold shifts including (1) recovery of the cochlea from a temporary pathology caused by the deafening and/or implantation procedures, (2) effects of electrical stimulation on the auditory pathway, and (3) tissue growth in the implanted cochlea. They also suggest that surviving hair cells influence electrical threshold levels.

Hypoaesthesia occurs with sensory hypersensitivity in chronic whiplash – Further evidence of a neuropathic condition

Hypersensitivity to a variety of stimuli has been shown in whiplash associated disorders and may be indicative of peripheral nerve involvement. This cross-sectional study utilised Quantitative sensory testing (QST) including vibration, thermal, electrical detection thresholds as an indirect measure of primary afferents that mediate innocuous and painful sensation. Pain thresholds and psychological distress (SCL-90-R) were also measured. Thirty-one subjects with chronic whiplash (>3 months, NDI: 49 ± 17) and 31 controls participated. The whiplash group demonstrated elevated vibration, heat and electrical detection thresholds at most hand sites compared to controls ( p < 0.05). Electrical detection thresholds in the lower limb were no different from controls ( p = 0.83). Mechanical and cold pain thresholds were lower in the whiplash group ( p < 0.05) with no group difference in heat pain thresholds ( p > 0.1). SCL-90 scores were higher in the whiplash group but did not impact on any of the sensory measures. A combination of pain threshold and detection measures best predicted the whiplash group. Sensory hypoaesthesia and hypersensitivity co-exist in the chronic whiplash condition. These findings may indicate peripheral afferent nerve fibre involvement but could be a further manifestation of disordered central pain processing.

Evidence of chorda tympani dysfunction in patients with burning mouth syndrome

More than two-thirds of patients with burning mouth syndrome (BMS) have altered taste sensation. The authors conducted a study to assess chorda tympani and trigeminal nerve function in these patients. The study was composed of 48 patients; 22 were diagnosed as having BMS, 14 had burning symptoms related to other diseases and were diagnosed as having secondary burning mouth syndrome (SBMS), and 12 were healthy volunteers. The authors evaluated the electrical detection thresholds of the infraorbital and mental nerves and the electrical taste and electrical detection/tingling thresholds in the anterior two-thirds of the tongue for all patients. Electrical taste threshold is thought to be dictated by chorda tympani nerve function while electrical detection/tingling thresholds are regulated by trigeminal nerve function. The mean electrical taste/tingling detection thresholds ratio and the taste detection thresholds were significantly higher in patients with BMS than in patients with SBMS and in control subjects, indicating chorda tympani nerve dysfunction. Eighteen (82 percent) of the 22 patients with BMS demonstrated chorda tympani dysfunction (13 unilateral and five bilateral). Chorda tympani hypofunction may play an important role in BMS pathology. Unilateral hypofunction may be sufficient to produce generalized burning sensation exceeding the affected nerve area. Elevated taste detection threshold levels determined via electrogustatory testing and an elevated taste/tingling detection thresholds ratio may assist clinicians in the diagnosis of BMS. More studies are needed to validate these findings.

11th International Dental Congress on Modern Pain Control The Essential Role of Dental Anesthesiology in the 21st Century Safe and Comfortable Dentistry 4th–7th October, 2006

11th International Dental Congress on Modern Pain Control The Essential Role of Dental Anesthesiology in the 21st Century Safe and Comfortable Dentistry 4th–7th October, 2006

GABAergic modulation of diffuse noxious inhibitory controls (DNIC): a test by use of lorazepam

Diffuse noxious inhibitory controls (DNIC) are an important supra-spinal mechanism of pain inhibition. Neurotransmitters and modulators involved in DNIC are serotonin and endogenous opioids. The influence of substances binding to the GABA(A) receptor complex, which has been suggested to play an important role in descending pain inhibition on DNIC has not yet been investigated. The aim of the present study was to find out whether the inhibitory action of DNIC might also be mediated by GABAergic mechanisms. Therefore, DNIC modulation via GABAergic mechanisms was studied in a double blind, placebo-controlled crossover design by oral application of 0.02 mg/kg(body weight )lorazepam in 20 healthy subjects. DNIC inhibition was induced by heterotopically administered tonic heat. The inhibitory effect was assessed by use of a multiple staircase method, measuring electrocutaneous detection, and pain thresholds in parallel. Concurrent tonic heat stimuli, at both painful and non-painful levels, significantly increased the electrical pain threshold whereas the electrical detection threshold was not affected. This pain-specific inhibitory effect did not differ significantly between sessions with lorazepam and placebo. Accordingly, lorazepam did not modify the inhibitory action of DNIC although lorazepam generally increased heat pain threshold. The results of the present study provided no evidence for DNIC being mediated by activation of the GABA(A) receptor complex.

Impairment of pain inhibition in chronic tension-type headache

Evidence has been accumulated suggesting that a dysfunction in pain inhibitory systems, i.e. in ‘diffuse noxious inhibitory controls‘ (DNIC)-like mechanisms, might be—amongst other factors—responsible for the development of anatomically generalized chronic pain like fibromyalgia. The aim of the present study was to look for similar impairments in chronic tension-type headache (CTTH) as a regionally specific pain syndrome. Twenty-nine CTTH patients and 25 age- and sex-matched healthy control subjects participated in the study. After baseline assessment of electrical detection and pain thresholds, tonic heat stimuli were concurrently applied by a thermode to the thigh to induce DNIC-like pain inhibition. Tonic heat stimuli were applied either slightly above (‘pain’ condition) or slightly below (‘heat’ condition) pain threshold. For determination of electrical detection and pain thresholds, electrocutaneous stimuli were administered either to the forearm (extra-cranial site) or to the temple (cranial site), using a multiple staircase procedure. The increase in the electrical detection and pain thresholds induced by concurrent tonic heat stimulation was significantly smaller in the CTTH patients than in the control subjects. This group difference was present during the ‘pain’ as well as the ‘heat’ condition. Furthermore, the electrical detection and pain thresholds were affected in this group-specific manner both at the forearm and at the temple. These findings suggest that patients with CTTH suffer from deficient DNIC-like pain inhibitory mechanisms in a similar manner, as do patients with anatomically generalized chronic pain like fibromyalgia.