Per Skjelbred

Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain

&NA; We examined the analgesic effect of racemic ketamine and its 2 enantiomers in 16 female patients (age: 20–29 years) suffering acute pain after oral surgery and in 7 female patients (age: 42–79 years) suffering chronic neuropathic orofacial pain. All 3 forms of ketamine consistently relieved postoperative pain, (S)‐ketamine being 4 times more potent than (R)‐ketamine. The analgesic effect was maximal 5 min after i.m. injection and lasted for about 30 min. The 7 patients with neuropathic pain received ketamine at one or several occasions. Four patients (age: 54–79 years) who had suffered pain for more than 5 years did not experience an analgesic effect, whereas 3 patients (age: 42–53 years) who had suffered pain for less than 3 years reported pain relief lasting from 24 h to 3 days. The individual type of response did not depend on the form of ketamine used. The mental side effects were qualitatively similar for the 3 forms of ketamine. Relative to the analgesic effect (S)‐ketamine caused more disturbing side effects than did (R)‐ketamine. The mean serum concentration of each form of ketamine at the time of maximal effect was close to the approximate Kd value for PCP site occupancy by that particular form. This is in concert with the hypothesis that the effect of ketamine on acute nociceptive pain is due to N‐methyl‐D‐aspartate (NMDA) receptor inhibition and adds to the evidence that NMDA receptors are important for the perception of acute, nociceptive pain in humans. The lack of analgesic effect of ketamine in patients who had suffered neuropathic pain for several years shows that NMDA receptors are not involved in the perception of all types of pain and indicates that NMDA receptors become less important for pain perception in older patients with a long pain history. The atypical (prolonged) analgesic effect of ketamine in patients who had suffered neuropathic pain for less than 3 years may be a placebo effect, but the possibility that this effect reflects a permissive role of NMDA receptors during the development of neuropathic pain cannot be excluded.

Effect of homoeopathy on pain and other events after acute trauma : placebo controlled trial with bilateral oral surgery

Abstract Objective: To examine whether homoeopathy has any effect on pain and other inflammatory events after surgery. Design: Randomised double blind, placebo controlled crossover trial with “identical” oral surgical procedures performed on two separate occasions in 24 patients. Interventions: Treatment started 3 hours after surgery with either homoeopathy or placebo. Main outcome measures: Postoperative pain and preference for postoperative course assessed by patients on visual analogue scales. Measurements of postoperative swelling and reduction in ability to open mouth. Assessment of bleeding after surgery. Results: Pain after surgery was essentially the same whether treated with homoeopathy or placebo. Postoperative swelling was not significantly affected by homoeopathy, but treatment tended to give less reduction in ability to open mouth. No noticeable difference was seen in postoperative bleeding, side effects, or complaints. Thirteen of the 24 patients preferred the postoperative course with placebo. Conclusions: No positive evidence was found for efficacy of homoeopathic treatment on pain and other inflammatory events after an acute soft tissue and bone injury inflicted by a surgical intervention. Differences in the order of 30% to 40% would have been needed to show significant effects. Key messages Key messages This crossover trial studied the effects of homoeopathy on pain and other events of removal of impacted wisdom teeth Remarkably similar assessments of pain were observed with homoeopathy and placebo No positive evidence could be found for homoeopathic effects

Analgesic efficacy of acetaminophen 1000 mg, acetaminophen 2000 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg versus placebo in acute postoperative pain.

Acetaminophen (APAP) 1000 mg, APAP 2000 mg, the combination of APAP 1000 mg plus codeine phosphate 60 mg (APAPCOD), and placebo (PBO) were compared in a 6‐hour, randomized, single‐dose, double‐blind, parallel‐group analgesic trial. All active treatments were statistically superior (p<0.05) to placebo for 4 hours after medication with respect to pain intensity (PI) and pain intensity difference (PID), and up to 3 hours regarding pain relief (PAR). The combination scored better than all other treatments on the summary analgesic efficacy measures sum PI (SUMPI), sum PID (SPID), and total PAR (TOTPAR). The combination was statistically superior to APAP 1000 mg on SUMPI, TOTPAR and maximum PAR (MAXPAR). Acetaminophen 2000 mg showed marginal numerical superiority over 1000 mg for SUMPI, but was not statistically superior for any summary efficacy measure. The 2000‐mg dose was numerically inferior to APAPCOD for every summary efficacy measure and statistically inferior regarding SPID and MAXPAR. We concluded that codeine 60 mg added to acetaminophen 1000 mg offers analgesic advantages, and acetaminophen reaches an analgesic ceiling effect at 1000 mg using the dental pain model.

Short-Term Association between Anxiety, Self-Medication and Subjective Postoperative Clinical Signs in Norwegian Patients Following Surgical Removal of Third Molar Teeth

Statement of Problem:Gender moderates pain experience where females had a lower pain threshold and were less tolerant to pain thanmales. Less is known about postoperative self-medication and swelling. Purpose: The purpose of this pilot trial was to investigate if gender could influence the association between preoperative dental anxiety, postoperative analgesic tablet consumption and pain in Norwegian patients during a 7 day period following third molar surgery. Materials and Methods: Twenty-seven (15 females/ 12 males) consecutive Norwegian patients of ASA class I-II participated. Mean ages (SD) females/males were 29.5 (7.4)/32.7 (10.7) years, heights were 168.6 (5.4)/ 179.9 (6.0) cm, and weights were 59.3 (7.2)/80.7 (12.2) kg. A single third molar with at least one previous history of acute pericoronitis was removed using a buccal envelope flap and local anesthesia (lidocaine 2% + adrenalin 1:80 000) only. Patient consent and Norwegian Ethical Committee approval was obtained prior to trial. The patients scored their level of dental anxiety on Corah’s Dental Anxiety Scale (CDAS) just prior to surgery, and their subjective pain intensity (PI) every hour up to 12 hours after completing surgery, including the exact time patients took analgesic drugs for the first time on a 0-10 numerical rating scale (NRS). PI was scored at 8:00, 12:00, 16:00 and 20:00 hours every day for 6 days after the day of surgery. The patients had access to OTC analgesics ad libitum restricted only by the maximum daily dose regimen specific of each drug. Every tablet intake including type and dose during the observation period was noted. Data Analysis: Mean group data including specifics of the surgical procedures were calculated. Differences between data were analyzed by the Independent Samples T-Test, and Pearson’s correlation coefficients were computedwith theBivariateCorrelationsTest (IBMÂ SPSSÂ Statistics release 20.0.0). The level of 2-tailed statistical significance was P<0.05, and equal variances were not assumed for group data. Results: Mean (SD) females/males time of the day when surgery ended was 12:49 (2:05)/11:41 (2:18) hours. The corresponding volumes of local anesthetic were 2.7 (0.27)/3.2 (0.5) ml. Times used for obtaining effect of local anesthetic were 2.2 (1.3)/4.5 (4.1) min, and times used for surgery were 16:32 (8:39)/15:05 (5:35) min:sec. Females and males differed with respect to height and weight (P=0.000), and volume of local anesthetic used (P=0.029). The numerical difference in time for local anesthetic effect was not statistically significant (P=0.88). CDAS scores were 8.5 (3.3)/7.4 (2.6), times to first drug intake 2:50 (2:26)/3:35 (2:02) hrs:min, PI at the first drug intake 4.8 (2.9)/4.7 (2.1), sum tablets over