Biomedical subjects

Jesper Dirks

Publications and source records attributed to Jesper Dirks.

5 recordsLinked to original sources

PubMed2005

Intravenous dextromethorphan to human volunteers: relationship between pharmacokinetics and anti-hyperalgesic effect.

The aim of this study was to investigate the effect of dextromethorphan (DM) 0.5 mg/kg administered intravenously (i.v.) on hyperalgesia and pain after a tissue injury in human volunteers, and to describe the relationship between pharmacokinetic and pharmacodynamic data. The heat-capsaicin sensitisation model, a well-established experimental hyperalgesia model was induced in 24 healthy, male volunteers aged 21-35 years. The subjects received i.v. DM 0.5 mg/kg or isotonic saline on two separate study sessions. The primary outcome measure from 0 to 3 h was reduction in area of established secondary hyperalgesia. Secondary outcome measures were reduction in area of secondary hyperalgesia in response to brief thermal stimulation, heat pain detection thresholds and painfulness after tonic heat pain. Blood samples were collected throughout the study to describe the relationship between pharmacokinetic and pharmacodynamic data. Intravenous DM 0.5 mg/kg significantly reduced areas of established secondary hyperalgesia with an average of 39% (P<0.05). Development of secondary hyperalgesia was substantially prevented by DM (P<0.05). No significant effect was seen on either heat pain detection thresholds or after tonic heat pain. The pharmacokinetic-pharmacodynamic relationship showed a large inter-subject variation with a mean delay in effect of nearly 2 h in relation to peak serum concentration. The results strongly indicate that DM is an anti-hyperalgesic drug. The delay in effect may be explained by several mechanisms and suggests that timing of DM administration is an essential factor for using the drug in clinical settings.

Adolescent↗

PubMed2003

The heat/capsaicin sensitization model: a methodologic study.

The heat/capsaicin sensitization model induces cutaneous sensitization by using a combination of heat and topical capsaicin. It has been suggested that the stability and duration of the cutaneous sensitization are due to a synergistic effect between heat and capsaicin. The aim of this study was to evaluate a possible synergistic effect between heat and capsaicin in inducing cutaneous sensitization. Twenty healthy male volunteers completed this random order, 4-session study. Three different stimulation combinations were used to induce cutaneous sensitization: day A, heat and capsaicin; day B, heat alone; day C, capsaicin alone. Combination A was repeated on day D to determine between day reproducibility. Rekindling was performed 3 times at 40-minute intervals to maintain stable areas of secondary hyperalgesia. Brief thermal sensitization (45 degrees C for 3 minutes) was induced at each session. Within and between day reproducibility was calculated. There was no difference between the size of areas of secondary hyperalgesia after stimulation with heat/capsaicin compared to heat and capsaicin stimulation alone. The within day reproducibility was better with heat/capsaicin than with either stimulation alone. There was no synergistic or additive effect between heat and capsaicin in inducing cutaneous sensitization. Rekindling seems to be the important factor in maintaining stable and long-lasting cutaneous sensitization.

Adolescent↗

PubMed2002

Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization.

BACKGROUND: The anticonvulsant gabapentin, proven effective for neuropathic pain in two large, placebo-controlled clinical trials, is widely used for treatment of chronic pain. Preclinical studies have demonstrated analgesic and antiallodynic effects in models involving neuronal sensitization and nerve injury, without affecting acute pain transmission. The aim of the present study was to link data from animal models and clinical trials for chronic pain by investigating the effect of gabapentin on acute nociception and experimentally induced cutaneous hyperalgesia in healthy volunteers. METHODS: The human experimental hyperalgesia model, the heat-capsaicin sensitization model, was induced in 25 healthy male volunteers. Subjects received oral gabapentin (1,200 mg) or placebo after heat-capsaicin sensitization was established on the forearm. The primary outcome measures were the sizes of the areas of secondary hyperalgesia to von Frey hair and brush stimulation on the forearm. Secondary outcome measures were as follows: (1) size of secondary hyperalgesia area in response to brief thermal sensitization procedure on the thigh; (2) heat pain detection thresholds in normal and sensitized skin; and (3) painfulness of 1 min of 45 degrees C stimulation in normal skin. RESULTS: Oral gabapentin profoundly suppressed established cutaneous sensitization on the forearm and prevented development of cutaneous sensitization on the thigh. Thermal nociception in normal skin was unchanged. Side effects were modest. CONCLUSION: The results link preclinical findings with results from clinical trials of neuropathic pain. The results further suggest that gabapentin may prove effective in acute pain disorders involving neuronal sensitization, such as postoperative pain and acute herpetic pain, and could prove effective in prevention of chronic pain.

Acetates↗

PubMed2002

A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy.

BACKGROUND: The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy. METHODS: In a randomized, double-blind, placebo-controlled study, 70 patients received a single dose of oral gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest and during movement, and side effects were assessed on a four-point verbal scale 2 and 4 h postoperatively. RESULTS: Thirty-one patients in the gabapentin group and 34 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from a median of 29 (interquartile range, 21-33) to 15 (10-19) mg (P< 0.0001). Pain during movement was reduced from 41 (31-59) to 22 (10-38) mm at 2 h postoperatively (P < 0.0001) and from 31 (12-40) to 9 (3-34) mm at 4 h postoperatively (P = 0.018). No significant differences between groups were observed with regard to pain at rest or side effects. CONCLUSION: A single dose of 1,200 mg oral gabapentin resulted in a substantial reduction in postoperative morphine consumption and movement-related pain after radical mastectomy, without significant side effects. These promising results should be validated in other acute pain models involving central neuronal sensitization.

Acetates↗

PubMed2002

Mechanisms of postoperative pain: clinical indications for a contribution of central neuronal sensitization.

BACKGROUND: The relative importance of different nociceptive mechanisms for the intensity, duration, and character of postoperative pain is not well established. It has been suggested that sensitization of dorsal horn neurones may contribute to pain in the postoperative period. We hypothesized that wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia share a common mechanism, sensitization of central neurones, and consequently, that the short-acting opioid remifentanil would have comparable effects on hyperalgesia in both conditions. METHODS: In a randomized, controlled, double-blind trial, we assessed mechanical hyperalgesia in skin bordering the surgical wound, and an area of experimentally heat-induced secondary hyperalgesia on the thigh, in 12 patients who underwent abdominal hysterectomy within 5 days prior to the investigation. Observations were made before and during a drug challenge with remifentanil, which has been demonstrated to reduce the area of heat-induced secondary hyperalgesia in volunteers. RESULTS: The area of skin with surgically-induced mechanical hyperalgesia, the area of heat-induced secondary hyperalgesia, and pain during cough, were significantly reduced during remifentanil infusion compared with placebo (P = 0.008, P = 0.006, and P = 0.002, respectively). The relative reduction (% of baseline) of the area of skin with surgically-induced hyperalgesia and heat-induced secondary hyperalgesia during infusion of remifentanil was significantly associated (R2 = 0.72, P = 0.001). CONCLUSIONS: Although remifentanil is not a highly targeted "antihyperalgesic," these results support the hypothesis that both wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia may share common mechanisms, and that central neuronal sensitization may contribute to some aspects of postoperative pain. Antihyperalgesic drugs should be further developed and evaluated in clinical trials of postoperative pain.

Adult↗