Submaximal Effort Tourniquet Test Research Articles

Attenuation of tourniquet-induced pain in man by D-phenylalanine, a putative inhibitor of enkephalin degradation.

The effect D-phenylalanine (DPA), a putative inhibitor of enkephalin degradation, on the two separate pain components produced by the submaximal effort tourniquet test was evaluated in healthy human volunteers (N = 8). DPA attenuated the increase of the intensity of the ischemic and pressure pain components with increasing ischemia duration, but only the effect on the pressure pain component was significant. The results support some earlier reports suggesting that DPA has analgetic properties.

Plasma β-endorphin during clinical and experimental ischaemic pain

An improved radio-immunoassay using an antiserum directed towards the N-terminal part of the endogenous opioid peptide beta-endorphin 1-31 (beta-EP) was validated and applied to a study of beta-EP in plasma during ischaemic pain. Experimental ischaemic pain induced in seven healthy volunteers by the submaximal effort tourniquet test did not change plasma beta-EP or adrenocorticotrophin. Plasma beta-EP was determined in 21 patients with acute myocardial infarction (AMI) and in seven patients with unstable angina pectoris. Plasma beta-EP was 4.9 fmol/ml with 95% confidence limits, 3.2-7.8 fmol/ml in AMI patients at admittance, and 2.9 (2.0-3.4) fmol/ml one week later in stable and pain-free condition (p less than 0.05). The level in 49 healthy persons was 2.8 (2.4-2.9) fmol/ml. Elevated beta-EP levels were found in five AMI patients with cardiogenic shock and in four AMI patients dying within 24 h after admittance compared to the rest of AMI patients (p less than 0.02). beta-EP was not elevated during unstable angina pectoris, although pain scores were similar to AMI. The AMI group revealed a significant, although weak, positive correlation between plasma beta-EP and pain score (Spearman r = 0.49, p less than 0.05), while there was no correlation during unstable angina pectoris. beta-EP was not correlated to the amount of morphine required within the 48 h after admittance of AMI patients. We conclude that the increase of beta-EP in plasma during AMI may be due to stressful factors other than ischaemic pain and that it is questionable whether beta-EP in plasma is related to antinociception.

The effects of naloxone on opiate and placebo analgesia in healthy volunteers

Two double blind cross-over studies were performed using a submaximal effort tourniquet test (SETT) in healthy volunteers to investigate the role of endogenous opioids in placebo analgesia. In the first study IV naloxone significantly inhibited analgesia, miosis and sedation produced by the opioid dipipanone 10 mg in 12 subjects. In the second naloxone, which did not produce hyperalgesia, failed to inhibit significant placebo analgesia in 12 subjects. The results do not support the involvement of endogenous opioids in ischemic limb pain or placebo analgesia under these conditions.

Two separate components of pain produced by the submaximal effort tourniquet test

Human subjects could discriminate two separate components of pain during the submaximal effort tourniquet test. Since the effect of several test parameters was different on these two pain components it is suggested that attention would be paid to the discrimination of these pain components in the future studies with this methodology.

A modified submaximal effort tourniquet test for evaluation of analgesics in healthy volunteers

Three double blind, placebo controlled, cross-over studies were conducted to assess the activity of analgesics in healthy volunteers using a modified submaximal effort tourniquet test (SETT). On each study day tests were performed in a silent cubicle at 21°C immediately before and then hourly after drug administration. After exsanguination of the dominant arm trained subjects performed intermittent, isometric hand-grip exercise for 1 min and then rated pain intensity continuously on a visual analogue scale generated and scored by microcomputer. Tests were terminated by the subjects when pain became unbearable. Tourniquet times and cumulative analgesia scores were significantly increased by small doses of opiates, dipipanone and codeine but not by aspirin, indomethacin or diazepam. Scores on visual analogue scales for alertness and reports of side effects as well as the absence of analgesic activity of diazepam showed that analgesia was not related to sedation. The computerisation of pain ratings and standardisation of experimental conditions probably account for the sensitivity of this model. The difference between responses to opiates and anti-inflammatory drugs is discussed.

Naloxone inhibition of opiate analgesia in the submaximal effort tourniquet test

(SPON: J. Chamberlain) Dept. Clinical Pharmacology, Wellcome Research Labs., Beckenham, Kent, England

Failure of Transcutaneous Electrical Stimulation to Alleviate Experimental Tourniquet Pain

It has been proposed that transcutaneous electrical nerve stimulation (TENS) acts by stimulation of large nerve fibers which inhibits further propagation of nociceptive input conducted along smaller C-nerve fibers. We evaluated the effectiveness of TENS in alleviation of ischemic pain (C-fiber mediated) experimentally produced by the submaximal-effort tourniquet test. Cutaneous electrodes were placed proximal to the tourniquet and TENS was begun prior to exsanguination of the arm. Time from inflation of the tourniquet to onset of intolerable pain was noted together with a visual analog-derived intensity of pain for 10 subjects studied on three separate occasions. The results showed no statistically significant prolongation in the duration of ischemia tolerated nor reduction in the subjective intensity of pain during either single- or dual-channel stimulation in comparison to control levels.

PHARMACOKINETICS AND ANALGESIC EFFECTS OF I.M. AND ORAL KETAMINE

The pharmacokinetics and analgesic effects of i.m. and oral ketamine in a dose of 0.5 mg kg-1 were determined in six healthy volunteers. Analgesia was measured by the submaximal effort tourniquet test. Following both routes of administration, ketamine prolonged the period of pain-free ischaemic exercise. Pain thresholds were increased at 15 min and 30 min after i.m. injection and at 30 min after oral ketamine. The plasma ketamine concentration associated with analgesia was 150 ng ml-1 following the i.m. dose, but only 40 ng ml-1 after the oral dose. Oral administration was, however, associated with much greater concentrations of the metabolite norketamine, which may have contributed to the analgesic effect.

PHARMACOKINETICS AND ANALGESIC EFFECT OF KETAMINE IN MAN

The pharmacokinetics and analgesic effect of i.v. ketamine in doses of 125 microgram kg-1 and 250 microgram kg-1 were determined in five healthy volunteers. Analgesia was measured with the submaximal effort tourniquet test. Both doses of ketamine prolonged the period of pain-free ischaemic exercise while the plasma ketamine concentration was greater than 100 ng ml-1. Ketamine was distributed rapidly (T 1/2 alpha = 17 min). The elimination half-life was 186 min.

Transcutaneous electrical nerve stimulation and the reaction to experimental pain in human subjects.

The effect of peripheral transcutaneous electrical nerve stimulation (TENS) on the reaction to experimental pain in human volunteers has been assessed. Placebo stimulation and electrical stimulation at moderate intensities failed to modify the response to the pain produced by conducted thermal stimuli. TENS at very high intensities did however elevate both the thermal pain threshold and the tolerance temperature. TENS at moderate intensities failed completely to alter the response to graded mechanical stimuli. The subjective pain assessment and the maximum pain tolerance produced by ischaemic pain after a submaximal effort tourniquet test were significantly modified by peripheral electrical stimulation at non-noxious intensities. The response to experimental pain can therefore be altered in man by peripheral electrical stimulation in a manner partly dependent on the sensory modality used for producing the experimental pain and on the intensity of the electrical stimulation.

The submaximal effort tourniquet test: its use in evaluating experimental and chronic pain.

The submaximal effort tourniquet test has been widely used to evaluate experimental and chronic pain; however, there has been great variation in the manner in which the test has been applied. The present study systemitically evaluates how different levels of exercise duration and effort affect subjects' report of pain. The data indicate the following: (1) the manner in which the exercise is performed has an important effect on subjects' rating of pain, and (2) under all conditions studied, the pain ratings do not increase as a linear function of time. Both findings warrant precautions when using the submaximal effort tourniquet test to study experimental and chronic pain.