T2 * relaxation time in Achilles tendinosis and controls and its correlation with clinical score.

PURPOSE: To investigate if the T2 * of Achilles tendons can discriminate between chronic Achilles tendinosis and healthy controls; to correlate with clinical score; to evaluate its short-term repeatability; and to estimate minimal detectable change. MATERIALS AND METHODS: Twenty patients, with chronic mid-portion Achilles tendinosis, and 10 controls without history of Achilles tendon symptoms, were examined with a 3T MR scanner with a 3D flash ultrashort time to echo sequence with five different echo times. The sequence was run twice to test repeatability. The tendon border was delineated on axial slices at three different levels in the calculated T2 * maps. The clinical severity of Achilles tendinosis was measured by a VISA-A questionnaire. RESULTS: There was a significant difference in mean T2 * between symptomatic and control tendons (P < 0.001). In patients with unilateral symptoms no significant difference in T2 * was found between symptomatic and contralateral asymptomatic tendons (P = 0.19). There was no significant correlation between clinical severity and T2 * (r = -0.28, P = 0.22). The short-term repeatability of T2 * showed a coefficient of variation of 18%, a least significant change of 50%, and the intraclass correlation coefficient had an average consistency of 0.99. CONCLUSION: T2 * may help to differentiate between chronic Achilles tendinosis and healthy controls but was not associated with the clinical score. However, and notably, the reproducibility of the method was low and the number of patients was small. J. Magn. Reson. Imaging 2016;43:1417-1422.

Reduction of human experimental muscle pain by alfentanil and morphine.

Musculoskeletal pain is a major clinical problem. By using various experimental models in humans, the understanding of the basic mechanisms behind muscle pain can increase, thereby giving hope for new and optimized treatment. Opioids are increasingly often used to treat muscle pain. There are, however, a limited number of previous studies on opioids and muscle pain, most of them using a relative low, single dose. Therefore, we wanted to further study the effect of two rather high doses of alfentanil (25 and 75ng/ml) and morphine (0.14 and 0.28mg/kg) in human volunteers. The study consisted of two parallel studies with morphine and alfentanil, respectively, and was conducted as randomized, double-blinded, placebo-controlled, 3-way cross-over. We used intramuscular infusion of hypertonic saline and intramuscular electrical stimulation to induce experimental pain. Visual analog scale (VAS)-score, intramuscular electrical pain thresholds and pain area (local and referred) were measured. Both alfentanil and morphine at their highest doses induced a 6 to 7-fold increase in pain thresholds to single and repetitive (5 stimulations, 2Hz) electrical stimulation. Alfentanil and morphine also reduced VAS score about 4 to 5-fold during suprathreshold electric stimulation and during infusion of hypertonic saline. None of the drugs decreased referred pain. There were no apparent differences between the drugs, in terms of effect or adverse reactions. In conclusion, this is the first study to compare two high doses of alfentanil and morphine on experimental muscle pain in humans. Both alfentanil and morphine reduced experimental muscle pain. There were no indications of any true pharmacodynamic differences between the two drugs.

Dose-dependent effects of morphine on experimentally induced cutaneous pain in healthy volunteers.

This study examines the dose dependent analgesic effects of two doses of morphine and a single dose of alfentanil on experimentally induced cutaneous pain. In 16 healthy volunteers pain was induced by a skin burn injury and by continuous electrical skin stimulation. Mechanical pain thresholds (PT, von Frey filament), area of secondary hyperalgesia (SH) and 'wind-up like pain' upon repetitive stimulation (40-g load, 3Hz, 30s) were assessed. Analgesic effects on these pain parameters were tested at steady-state IV infusions of morphine, 50% (plasma concentration 15ng/ml) and 100% (plasma concentration 30ng/ml) of maximal tolerable dose to be given to healthy volunteers, and with an effective dose of alfentanil (plasma concentration 70ng/ml). All effects were compared to active placebo, midazolam infusion (20microg/kg for 10min). Alfentanil significantly diminished the SH area in the burn injury model as well as in the electrical pain model. Additionally, alfentanil increased PT several fold in both models. The high dose of morphine showed a similar analgesic response pattern as alfentanil even though the effects were only statistically significant in the electrical pain model. The low dose of morphine as well as placebo did not affect these pain parameters. 'Wind-up like pain' was not influenced by any of the given drugs. In conclusion, the present study clearly indicates dose dependent effects of morphine on experimentally induced cutaneous pain. The high dose of morphine (30ng/ml) was approximately equianalgesic to the administered alfentanil dose (70ng/ml).

The distribution of hyperaemia induced by skin burn injury is not correlated with the development of secondary punctate hyperalgesia.

UNLABELLED: This study in 20 volunteers examines whether changes in cutaneous blood flow distribution (laser Doppler flow scanning, LDS) and visible flare correlate in time and in distribution with the development of secondary hyperalgesia (SH, punctate stimulation of a 45-g von Frey filament) induced by a superficial skin burn injury. Areas of LDS and flare were at their largest at 5 minutes after the burn injury (58 +/- 30 and 20 +/- 11 cm2, respectively), whereas the largest area of SH was seen after 60 minutes (50 +/- 45 cm2). Although the maximum areas of LDS and SH were of the same magnitude, the blood flow response was essentially abolished when the maximal SH area was noticed at 60 minutes. Furthermore, on an individual basis, there was no correlation between the size of maximal LDS area (at 5 minutes) and maximal SH area (at 60 minutes) (r = 0.27; P =.26). Therefore, peripheral mechanisms associated with the neurogenic inflammation reaction surrounding a skin burn injury are not directly associated with the induction of SH. PERSPECTIVE: Tissue trauma and inflammation-induced sensory abnormalities are important because they are involved in acute nociceptive pain, as well as in chronic pain conditions. This study notes the significance of central sensitization for the development of secondary hyperalgesia, an important phenomenon underlying many clinical pain conditions.

The synergistic effect of combined treatment with systemic ketamine and morphine on experimentally induced windup-like pain in humans.

UNLABELLED: In this study, we evaluated whether combined treatment with ketamine (KET), an N-methyl-D-aspartate receptor antagonist, and morphine (MO) results in positive analgesic effects. Eleven volunteers were exposed to a skin burn injury on the leg. The effects of IV KET (9 microg. kg(-1). min(-1); 45 min) and MO (10 microg. kg(-1). min(-1); 10 min) alone and in combination, as well as placebo (saline; 10 min), were studied in a randomized, crossover, double-blinded design. The area of secondary hyperalgesia (SH) for mechanical stimulation was diminished by KET as compared with placebo. Mechanical pain thresholds were increased severalfold with KET and with KET plus MO, both in the primary hyperalgesic (PH; burn injury) and SH area. MO infusion showed no effect on the SH area or pain threshold. Windup-like pain was evaluated by continuous assessment on a visual analog scale during 30 s of repetitive stimulation (40-g load at 3 Hz) and analyzed as a sum of pain scores. The combined treatment (KET plus MO) almost abolished windup-like pain both in the PH and the SH areas, an effect that was not present with monotherapy with KET or MO. This study provides experimental support for a positive analgesic interaction between an N-methyl-D-aspartate receptor antagonist and an opioid on central summation of pain. IMPLICATIONS: This is the first experimental study in humans to find synergistic analgesic effects with coadministration of the N-methyl-D-aspartate receptor antagonist ketamine and morphine on pain involving central sensitization phenomena.