Lasse A. Skoglund

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.

Comparison of ketamine and pethidine in experimental and postoperative pain

&NA; The analgesic efficiency of ketamine and pethidine was compared in experimental ischemic pain and postoperative pain after oral surgery. Naloxone 1.6 mg or placebo was given 5 min before the analgesic drug. The subjects recorded their pain on a visual analogue scale. Both ketamine 0.3 mg/kg and pethidine 0.7 mg/kg were effective as analgesics against the two types of pain studied. Naloxone prevented the analgesic effect of pethidine, but had no effect on ketamine analgesia. The results are in accordance with the hypothesis that the analgesic effect of ketamine is mediated by a non‐opioid mechanism, possibly involving PCP‐receptor‐mediated blockade of the NMDA‐receptor‐operated ion channel.

Intravenous Acetaminophen (Paracetamol): Comparable Analgesic Efficacy, but Better Local Safety than Its Prodrug, Propacetamol, for Postoperative Pain After Third Molar Surgery

We compared an acetaminophen (paracetamol) 1 g (n = 51) formulation for infusion with propacetamol 2 g (n = 51) and placebo (n = 50) in a randomized, controlled, double-blind, parallel group trial in patients with moderate-to-severe pain after third molar surgery. Treatment efficacy was assessed in house for 6 h after starting the 15-min infusion. Significant effects versus placebo (P < 0.01) were obtained with both active treatments on pain relief, pain intensity difference on a 100-mm visual analog scale, and on a categorical scale (except for propacetamol at 6 h). No significant differences were noted between active groups except at 1 h. Six-hour weighted sums of primary assessments showed significantly better efficacy than placebo (P < 0.0001) and no difference between active treatments. Median stopwatch time to onset of pain relief for active treatment was 6–8 min after infusion start. Active treatments showed comparable efficacy with a significantly longer duration of analgesia and better patients’ global evaluation compared with placebo. The incidence of patients reporting local pain at the infusion site was significantly less frequent after IV acetaminophen or placebo (0%) in comparison with propacetamol (49%). In conclusion, acetaminophen 1 g and propacetamol 2 g were superior to placebo regarding analgesic efficacy, with a more frequent incidence of local pain at the infusion site for propacetamol.

Pain and discomfort experienced after placement of a conventional or a superelastic NiTi aligning archwire

Two nickel-titanium archwire types commonly used for initial tooth alignment were compared with regard to the pain/discomfort patients experience during the initial phase of tooth movement. The two archwires used were a superelastic nickel-titanium alloy, 0.014 inch Sentalloy, Light (GAC International Inc. Central Islip, NY, USA) and a 0.014 inch Nitinol (unitek, Monrovia, CA, USA), a conventional nickel-titanium aligning archwire.One hundred and twenty-eight consecutive patients attending an orthodontic university clinic and 2 private practices for routine placement of a fixed appliance were randomly assigned one of these 2 initial archwires. Assessments of pain/discomfort were made daily by means of a 100 mm visual analog scale (VAS) over the first 7-day period after bonding. On the first day, recordings were made every hour for the first 11 hours.The results showed that the level of discomfort increased continuously every hour after the insertion of either a Sentalloy or a Nitinol as first archwires, with a peak in the first night, remaining high on the second day and decreasing thereafter to baseline level after 7 days. During the first 10 hours it was apparent that the pain/discomfort experienced after placement of a Sentalloy was less than that found with the Nitinol archwire, although a significant difference could be found at 4 hours only. No significant gender-specific differences were found in either archwire group. A significant difference between the upper and lower dental arches was observed during the first 11 hours after placement of either a Sentalloy or a Nitinol archwire, with the lower arch having the higher pain experience.ZusammenfassungZwei verschiedene Bögen aus NiTi-Legierungen, die häufig für die initiale Nivellierung verwendet werden, wurden in Hinsicht auf das Auftreten von Schmerzen/Beschwerden zu Beginn der Zahnbewegung untersucht. Das eine Bogenmaterial war eine superelastische NiTi-legierung, 0,014 inch Sentalloy, Light (GAC International Inc., Central Islip, N. Y.), das andere ein herkömmlicher 0,014 inch Nitinol-Bogen (Unitek, Monrovia, Kalifornien).128 fortlaufend behandelte Patienten aus einer kieferorthopädischen Universitätsklinik und zwei privaten Praxen, bei denen routinemäßig eine Multibandapparatur eingesetzt werden sollte, wurden randomisiert für den einen oder den anderen Bogen vorgesehen. Die Beurteilungen der Schmerzen/Beschwerden wurden täglich während der ersten sieben Tage nach dem Einsetzen der festsitzenden Apparatur auf einer visuellen Skala von 100 mm Länge (visual analogue scale, VAS) vorgenommen. Zusätzlich wurde am ersten Tag für die ersten elf Stunden nach dem Einsetzen stündlich die Schmerzintensität aufgezeichnet.Die Ergebnisse zeigten, daß die Beschwerden für den ersten Bogen, sowohl für den Sentalloy-als auch für den Nitinol-Bogen, kontinuierlich jede Stunde nach dem Einsetzen anstiegen. Der Höhepunkt wurde in der ersten Nacht erreicht, blieb am zweiten Tag auf derselben Höhe und verringerte sich kontinuierlich bis zum siebten Tag auf das individuelle Ausgangsniveau. Während der ersten zehn Stunden war es offensichtlich, daß nach der Eingliederung der Bögen beim Sentalloy-Bogen deutlich geringere Beschwerden auftraten als bei dem Nitinol-Bogen; dieser Unterschied war jedoch nur für die ersten vier Stunden signifikant. Keine signifikanten Unterschiede der Beschwerden zwischen den Bogenmaterialien fanden sich hinsichtlich des Geschlechts der Patienten. Ein signifikanter Unterschied wurde zwischen dem Ober- und dem Unterkiefer während der ersten elf Studen nach dem Einsetzen sowohl des Sentalloy- als auch des Nitinol-Bogens beobachtet; im Unterkiefer traten deutlich stärkere Beschwerden auf.

Time to Onset of Analgesia and Analgesic Efficacy of Effervescent Acetaminophen 1000 mg Compared to Tablet Acetaminophen 1000 mg in Postoperative Dental Pain: A Single-Dose, Double-Blind, Randomized, Placebo-Controlled Study

This randomized, double‐blind, placebo‐controlled study compared the time to onset of analgesia and the analgesic efficacy of two formulations of acetaminophen 1000 mg—an effervescent solution and tablet—in 242 patients with moderate or severe pain following dental surgery. Onset of analgesia was determined using a two‐stopwatch procedure. Analgesia was assessed over a 4‐hour period. Treatments were compared using standard indexes of pain intensity and pain relief and summary measures. Both acetaminophen formulations were significantly more effective than their corresponding placebo for all efficacy assessments. The median time to onset of analgesia was significantly shorter with effervescent acetaminophen (20 minutes) compared to tablet acetaminophen (45 minutes). During the first 45 minutes after administration, effervescent acetaminophen was significantly more effective at each scheduled assessment time than tablet acetaminophen. The median time to meaningful pain relief was significantly shorter with effervescent acetaminophen (45 minutes) compared to tablet acetaminophen (60 minutes). At 4 hours after administration, the pain relief was significantly better with tablet acetaminophen than with effervescent acetaminophen. No other significant differences were observed between the active treatments. In conclusion, effervescent acetaminophen produces a significantly faster onset of analgesia than tablet acetaminophen.

Surgical management of 85 perforations to the maxillary sinus.

A study is presented of 85 cases of perforation to the maxillary sinus closed within 48 h after appearance. All cases were treated with the Rehrmann buccal flap procedure or primary suture. 1 patient developed an oro-antral fistula and sinusitis and a further 3 patients developed sinusitis postoperatively. A detailed presentation of the cases with complications is made. The relationship between a non-infectious sinus and the treatment results is discussed and the importance of antibiotic treatment in addition to surgical intervention is stressed.

Analgesic Dose‐Response Relationship of Ibuprofen 50, 100, 200, and 400 mg after Surgical Removal of Third Molars: A Single‐Dose, Randomized, Placebo‐Controlled, and Double‐Blind Study of 304 Patients

The purpose of this single‐dose, randomized, placebo‐controlled, and double‐blind study was to evaluate the analgesic dose‐response relationship of 50‐mg, 100‐mg, 200‐mg, and 400‐mg doses of ibuprofen after third molar surgery. Patients were instructed to take a single dose of either placebo or 50 mg, 100 mg, 200 mg, or 400 mg of ibuprofen when the postoperative pain was moderate to severe. Acetaminophen 500 mg was used as a rescue medication. Pain intensity, pain relief, and any possible adverse events were recorded on self‐administered questionnaires hourly for 6 hours after intake of study medication. If rescue medication was taken, the time of intake was registered. A total of 304 patients entered the study, and 258 complied with the protocol. A positive analgesic dose‐response relationship of 50‐mg, 100‐mg, 200‐mg, and 400‐mg doses of ibuprofen was observed when evaluated by pain intensity difference, sum of pain intensity difference, pain relief, total pain relief, and survival distribution of patients not taking rescue medication. Although significant pain relief was seen after a dose of 50 mg ibuprofen, ibuprofen 400 mg provided maximum pain relief and the longest duration of analgesic effect. Mild transient adverse events were reported by 6.8% of the patients. However, there was no significant difference in frequency between the placebo and 50 mg, 100 mg, 200 mg, and 400 mg ibuprofen dose groups.

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.

Naproxen 500 mg bid versus Acetaminophen 1000 mg qid: Effect on Swelling and Other Acute Postoperative Events after Bilateral Third Molar Surgery

A controlled, randomized, double‐blind crossover study, in which the patients acted as their own controls, was carried out to test the efficacy of naproxen 500 mg × 2 versus acetaminophen 1000 mg × 4 for 3 days on the postoperative course following third molar surgery. Acetaminophen reduced the mean swelling on the 3rd postoperative day by 22.4% (p = 0.023) compared to that after naproxen. On the 6th postoperative day, there was 20.9% less mean swelling with naproxen (p = 0.44), although the total swelling measurements were much less than those measured on the 3rd postoperative day. Summed pain intensity (SUMPI3.5–11) on the day of surgery revealed no statistically significant difference between the acetaminophen or naproxen regimen with the exception of 0.5 hours (p = 0.002) and 1 hour (p = 0.009) after first medication when acetaminophen gave less pain than naproxen. Since the drug regimens were different, summed PI for the first acetaminophen dose interval (SUMPI3.5–6) and the first naproxen dose interval (SUMPI3.5–9) was calculated. There was a tendency toward a statistically significant difference in favor of acetaminophen for SUMPI3.5–6 (p = 0.055) but no statistically significant difference (p = 0.41) between the treatments with respect to SUMPI3.5–9. Naproxen was statistically superior (p ≤ 0.002) to acetaminophen at 08:00, 12:00, and 16:00 hours on the 1st postoperative day and at 08:00 hours on the 2nd postoperative day, when the pain intensity level was lower than that on the day of surgery. A 3‐day acetaminophen regimen reduces acute postoperative swelling better than naproxen on the 3rd postoperative day after third molar surgery but not on the 6th postoperative day when the total swelling is less.

Ketoprofen 75 mg qid versus Acetaminophen 1000 mg qid for 3 Days on Swelling, Pain, and Other Postoperative Events after Third‐Molar Surgery

A randomized, double‐blind, within‐patient, crossover study was carried out after bilateral “identical” surgical procedures using local anesthesia only. A 3‐day tablet regime of racemic ketoprofen 75 mg or acetaminophen 1000 mg qid (x 4) was given starting 3 hours after surgery. Ketoprofen reduced objectively measured swelling 27.8% (p < 0.04) better than acetaminophen 3 days after surgery and 70.8% (p < 0.02) better than acetaminophen 6 days after surgery. The pain intensity (PI) was lower after ketoprofen than after acetaminophen from 2 to 6 hours after the first drug intake (all p‐values = 0.03). Sum PI during the first (SUMPI3.5–6, p = 0.003) and second dose intervals (SUMPI6.5–9, p = 0.007) was lower for ketoprofen than for acetaminophen but not different for the third dose interval (SUMPI9.5–11, p = 0.53). Ketoprofen was a more effective analgesic than acetaminophen on the day of surgery (SUMPI3.5–11, p = 0.005). There was no difference (p > 0.05) between the treatments with respect to mouth opening, drug preference, global evaluation, or adverse reports. Adverse reports included stomach pain and diarrhea in both treatment groups. Ketoprofen 75 mg x 4 for 3 days reduces subjectively assessed pain and objectively measured swelling (i.e., anti‐inflammatory effect) following third‐molar surgery.