Postoperative analgesic efficacy of nefopam after anorectal surgery: a retrospective observational study

Objective: To examine the effectiveness of nefopam on postoperative pain control after anorectal surgeries. Methods: We retrospectively reviewed the electronic medical records of patients who underwent anorectal surgeries from January 2019 to March 2022 at two medical centers. The data were divided into nefopam and conventional groups. The primary outcome was the number of patients who requested additional opioids in the 24-h postoperative period. The secondary outcomes were numeric rating pain scores (NRPS) within a 24-h postoperative period and analgesic drugs-related side effects. Results: Eighty-seven patients in the conventional group and 60 in the nefopam group were recruited. The nefopam group reported less additional opioid consumption than the conventional group in all dimensions of analysis, including overall, adjusted to anesthetic techniques and types of surgery. However, these did not reach statistical significance (P = 0.093). Only patients in the nefopam group who underwent hemorrhoidectomy under TIVA or spinal anesthesia significantly required fewer additional opioids (P = 0.016, 60% mean difference). Similarly, the 24-h postoperative morphine consumption was lower in the nefopam group (mean difference = -3.4, 95%CI: 0.72,6.08). Furthermore, significantly lower NRPS were reported in the nefopam group during the 12-18 h postoperative period (P = 0.009). On the other hand, analgesic drugs related side effects were similar in both groups. Conclusions: The administration of nefopam after major anorectal surgery is beneficially evident in reducing postoperative opioid requirements. (AU)

Preliminary screening of therapeutic drugs for phenylalanine hydroxylase deficiency / 中国基层医药

Objective:To screen new drugs for treatment of phenylalanine hydroxylase deficiency.Methods:From October 2019 to October 2020, virtual drug screening was performed in Center of Genetic Medicine, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University computer according to the characteristics of the binding ability of phenylalanine hydroxylase to drug spatial structure. Ten candidate drugs were screened from the FDA drug library (including 2 697 kinds of active pharmaceutical ingredients). A eukaryotic expression system was used to determine the effects of drugs on the activity of phenylalanine hydroxylase at the molecular level. Drug-sensitive mutants were screened.Results:Among the 10 candidate drugs, neoplasm hydrochloride, fluocinonide acetate and risperidone increased 23% [ t = 18.21, P < 0.001, vs. non-drug-treated phenylalanine hydroxylase group (i.e., only solvent and no drug added to the reaction system)], 21% ( t = 3.44, P < 0.05, vs. non-drug-treated phenylalanine hydroxylase group), 31% ( t = 19.57, P < 0.001, vs. non-drug-treated phenylalanine hydroxylase group) of the activity of phenylalanine hydroxylase. The remaining drugs exhibited weak even inhibitory effects on the activity of phenylalanine hydroxylase. 25% of p.D101N mutant could be activated by risperidone ( t = 15.86, P < 0.001, vs. non-drug-treated p.D101N mutant group). Conclusion:Neoplasm hydrochloride, fluocinonide acetate and risperidone can be used as potential therapeutic drugs for phenylalanine hydroxylase deficiency, and p.D101N mutant can be used as the drug-sensitive mutation site.

Effects on postoperative nausea and vomiting of nefopam versus fentanyl following bimaxillary orthognathic surgery: a prospective double-blind randomized controlled trial

BACKGROUND: Postoperative nausea and vomiting (PONV) frequently occurs following bimaxillary orthognathic surgeries. Compared to opioids, Nefopam is associated with lower incidences of PONV, and does not induce gastrointestinal tract injury, coagulopathy, nephrotoxicity, or fracture healing dysfunction, which are common side effects of Nonsteroidal anti-inflammatory drugs. We compared nefopam- and fentanyl-induced incidence of PONV in patients with access to patient-controlled analgesia (PCA) following bimaxillary orthognathic surgeries. METHODS: Patients undergoing bimaxillary orthognathic surgeries were randomly divided into nefopam and fentanyl groups. Nefopam 120 mg or fentanyl 700 µg was mixed with normal saline to a final volume of 120 mL. Patients were given access to nefopam or fentanyl via PCA. Postoperative pain intensity and PONV were measured at 30 minutes and 1 hour after surgery in the recovery room and at 8, 24, 48, and 72 hours after surgery in the ward. The frequency of bolus delivery was compared at each time point. RESULTS: Eighty-nine patients were enrolled in this study, with 48 in the nefopam (N) group and 41 in the fentanyl (F) group. PONV occurred in 13 patients (27.7%) in the N group and 7 patients (17.1%) in the F group at 8 hours post-surgery (P = 0.568), and there were no significant differences between the two groups at any of the time points. VAS scores were 4.4 ± 2.0 and 3.7 ± 1.9 in the N and F groups, respectively, at 8 hours after surgery (P = 0.122), and cumulative bolus delivery was 10.7 ± 13.7 and 8.6 ± 8.5, respectively (P = 0.408). There were no significant differences in pain or bolus delivery at any of the remaining time points. CONCLUSION: Patients who underwent bimaxillary orthognathic surgery and were given nefopam via PCA did not experience a lower rate of PONV compared to those that received fentanyl via PCA. Furthermore, nefopam and fentanyl did not provide significantly different postoperative pain control.

Nefopam does not influence onset and recovery profiles of rocuronium-induced neuromuscular block: a prospective, double-blinded, randomized, controlled study

BACKGROUND: We investigated the hypothesis that pretreatment with nefopam 20 mg would influence the onset and recovery profiles of rocuronium-induced neuromuscular block. METHODS: After Institutional Review Board approval, 134 patients, aged between 20–65 years, belonging to the American Society of Anesthesiologists physical status classification I or II, were randomly allocated to receive either 0.9% normal saline (control group) or nefopam 20 mg (nefopam group), infused over one hour before induction of anesthesia. Anesthesia was induced with remifentanil and propofol, followed by endotracheal intubation with rocuronium 0.6 mg/kg. We recorded the lag time, onset time, clinical duration, recovery index, recovery time, and total recovery time. RESULTS: We included 111 patients in the final analysis. The lag time, onset time, clinical duration, recovery index, recovery time, and total recovery time of the nefopam group (n = 57) were not significantly different compared with that of the control group (n = 54). CONCLUSIONS: Pretreatment with nefopam 20 mg one hour before induction of anesthesia does not have a significant influence on the onset and recovery profiles of rocuronium-induced neuromuscular block.

Effects of nefopam on catheter-related bladder discomfort in patients undergoing ureteroscopic litholapaxy / 대한마취과학회지

BACKGROUND: Patients who undergo urinary catheterization may experience postoperative catheter-related bladder discomfort (CRBD). Previous studies have indicated that drugs with antimuscarinic effects could reduce the incidence and severity of CRBD. Accordingly, this study was carried out to investigate whether nefopam, a centrally acting analgesic with concomitant antimuscarinic effect, reduces the incidence and severity of CRBD. METHODS: Sixty patients with American Society of Anesthesiologists physical status I and II and aged 18–70 years who were scheduled to undergo elective ureteroscopic litholapaxy participated in this double-blinded study. Patients were divided into control and nefopam groups, comprising 30 patients each. In the nefopam group, 40 mg nefopam in 100 ml of 0.9% saline was administered intravenously. In the control group, only 100 ml of 0.9% saline was administered. All patients had a urethral catheter and ureter stent inserted during surgery. The incidence and severity of CRBD, numerical rating scale (NRS) score of postoperative pain, rescue pethidine dose, and side effects were recorded in the post-anesthesia care unit after surgery. RESULTS: The incidence (P = 0.020) and severity (P < 0.001) of CRBD were significantly different between the control group and the nefopam group. The NRS score of postoperative pain (P = 0.006) and rescue dose of pethidine (P < 0.001) were significantly higher in the control group than in the nefopam group. CONCLUSIONS: Intravenous administration of nefopam in patients scheduled to undergo ureteroscopic litholapaxy reduced the incidence and severity of CRBD, NRS score of postoperative pain and analgesic requirements.

Effects of warmed carrier fluid on nefopam injection-induced pain

BACKGROUND: Nefopam is a non-opioid, non-steroidal analgesic drug with fewer adverse effects than narcotic analgesics and nonsteroidal anti-inflammatory drugs, and is widely used for postoperative pain control. Because nefopam sometimes causes side effects such as nausea, vomiting, somnolence, hyperhidrosis and injection-related pain, manufacturers are advised to infuse it slowly, over a duration of 15 minutes. Nevertheless, pain at the injection site is very common. Therefore, we investigated the effect of warmed carrier fluid on nefopam injection-induced pain. METHODS: A total of 48 patients were randomly selected and allocated to either a control or a warming group. Warming was performed by diluting 40 mg of nefopam in 100 ml of normal saline heated to 31–32℃ using two fluid warmers. The control group was administered 40 mg of nefopam dissolved in 100 ml of normal saline stored at room temperature (21–22℃) through the fluid warmers, but the fluid warmers were not activated. RESULTS: The pain intensity was lower in the warming group than in the control group (P < 0.001). The pain severity and tolerance measurements also showed statistically significant differences between groups (P < 0.001). In the analysis of vital signs before and after the injection, the mean blood pressure after the injection differed significantly between the groups (P = 0.005), but the heart rate did not. The incidence of hypertension also showed a significant difference between groups (P = 0.017). CONCLUSIONS: Use of warmed carrier fluid for nefopam injection decreased injection-induced pain compared to mildly cool carrier fluid.

Adverse Hemodynamic Effects of Nefopam in Patients Undergoing Plastic and Aesthetic Surgery: A Single-Center Retrospective Study

BACKGROUND: Nefopam is used to improve postoperative hypothermia in the field of plastic and aesthetic surgery. However, there is a paucity of data about its adverse hemodynamic effects and safety. We therefore assessed its adverse hemodynamic effects in patients undergoing plastic and aesthetic surgery. METHODS: We conducted a single-center retrospective study of 148 patients, in whom we measured hemodynamic parameters using sphygmomanometry (systolic blood pressure [SBP], diastolic blood pressure [DBP], arterial blood pressure [ABP], and heart rate [HR]). Moreover, we also assessed myocardial oxygen demand using the rate pressure product (RPP). RESULTS: The patients included 96 men and 52 women, with a mean age of 34.7±8.5 years. There were no significant differences in SBP, DBP, ABP, HR, or RPP before and after nefopam administration (P>0.05). However, a significant difference was found in the number of the patients with an HR of >100 beats per minute or with an RPP of >12 U before and after nefopam administration (P=0.001). CONCLUSIONS: Surgeons should consider the possibility of tachycardia and increased blood pressure in the management of postoperative hypothermia in patients with cardiac arrhythmia, ischemic heart disease, or essential hypertension. Nonetheless, further prospective, large-scale, multi-center, randomized, controlled studies are warranted to confirm our results.

Concurrent Use of Nefopam vs. Ketorolac with Opioid Analgesic for Post-operative Pain Management

OBJECTIVE: To compare the analgesic effects and adverse drug reactions (ADRs) of fentanyl intravenous patient-controlled analgesia (ivPCA) with nefopam, a centrally acting analgesic agent with demonstrated opioid sparing activity, as compared to ketorolac in a tertiary teaching hospital. METHODS: A retrospective evaluation of electronic medical records was conducted on patient records including either nefopam or ketorolac with opioid ivPCA for post-operative pain management in general surgery department from January to December 2014. The status of pain control and ADRs were collected. RESULTS: Out of 6,330 general surgery cases, nefopam was given in 153 prescriptions (6.9%) and ketorolac in 81 prescriptions (3.6%). The level of pain control was not different between two groups (70.9% vs. 75.3%; p = 0.51), but ADRs were more frequently reported in nefopam group (9.8% vs. 2.5%; p < 0.05). New ADRs of hot flushes (n = 1) and paresthesia in hands (n = 1) were reported in nefopam group and they were unlisted in the approved package insert. No serious ADRs were reported in both groups. CONCLUSION: Our findings presented that nefopam showed a similar analgesic effect and higher ADR rates compared to ketorolac as an adjuvant to fentanyl iv PCA for postoperative pain management in general surgery patients in South Korea.

A comparison between ketorolac and nefopam as adjuvant analgesics for postoperative patient-controlled analgesia: a randomized, double-blind, prospective study / 대한마취과학회지

BACKGROUND: We compared the analgesic efficacy and side effects of ketorolac and nefopam that were co-administered with fentanyl via intravenous patient-controlled analgesia. METHODS: One hundred and sixty patients scheduled for laparoscopic cholecystectomy were randomly assigned to ketorolac (Group K) or nefopam (Group N) groups. The anesthetic regimen was standardized for all patients. The analgesic solution contained fentanyl 600 µg and ketorolac 180 mg in Group K, and fentanyl 600 µg and nefopam 120 mg in Group N. The total volume of analgesic solution was 120 ml. Postoperative analgesic consumption, recovery of pulmonary function, and pain intensities at rest and during the forced expiration were evaluated at postoperative 2, 6, 24, and 48 h. The postoperative side effects of analgesics were recorded. RESULTS: Cumulative postoperative analgesic consumptions at postoperative 48 h were comparable (Group K: 93.4 ± 24.0 ml vs. Group N: 92.9 ± 26.1 ml, P = 0.906) between the groups. Pain scores at rest and during deep breathing were similar at the time of each examination. The recovery of pulmonary function showed no significant differences between the groups. Overall, postoperative nausea and vomiting incidence was higher in Group N compared with Group K (59% vs. 34%, P = 0.015). The other side effects were comparable between both groups. CONCLUSIONS: Analgesic efficacies of ketorolac and nefopam that were co-administered with fentanyl for postoperative pain management as adjuvant analgesics were similar. However, postoperative nausea and vomiting incidence was higher in the nefopam-fentanyl combination compared with the ketorolac-fentanyl combination.

Post-operative intravenous patient-controlled analgesic efficacy of morphine with ketorolac versus nefopam after laparoscopic gynecologic surgery: a randomized non-inferiority trial / 대한마취과학회지

BACKGROUND: Nefopam is a non-opioid non-steroidal centrally acting analgesic. This study was conducted to assess the analgesic efficacy of intravenous patient-controlled analgesia (IV-PCA) using nefopam alone, compared with a combination of morphine and ketorolac, after laparoscopic gynecologic surgery. METHODS: Sixty patients undergoing laparoscopic gynecologic surgery received IV-PCA. Group A (n = 30) received IV-PCA with a combination of morphine 60 mg and ketorolac 180 mg, while group B (n = 30) received nefopam 200 mg (basal rate 1 ml/h, bolus 1 ml, and lockout time 15 min for both). The primary outcome evaluated was analgesic efficacy using the visual analogue scale (VAS). Other evaluated outcomes included the incidence rate of postoperative nausea and vomiting (PONV), patient satisfaction of pain control, percentage of patients requiring additional opioids, and incidence rate of postoperative adverse effects. RESULTS: Group B was not inferior to group A in relation to the VAS in the post-anesthesia care unit, and at 12, 24, and 48 h after surgery (mean difference [95% confidence interval], 0.50 [-0.43 to 1.43], -0.30 [-1.25 to 0.65], -0.05 [-0.65 to 0.55], and 0.10 [-0.55 to 0.75], respectively). The incidence rate of nausea was lower in group B than in group A at 12 and 24 h after surgery (P = 0.004 and P = 0.017, respectively). There were no significant differences in the other outcomes between groups. CONCLUSIONS: IV-PCA using nefopam alone has a non-inferior analgesic efficacy and produces a lower incidence of PONV in comparison with IV-PCA using a combination of morphine and ketorolac after laparoscopic gynecologic surgery.

Affinity capiIIary monoIith in the study of interaction between bovine serum aI-bumin and nefopam enantiomers / 中国药科大学学报

A pepsin modified poly (glycidyl methacrylate-ethyleneglycol dimethacrylate)(poly (GMA-EDMA)) capillary monolith (32 cm ×75 μm,22cm effective lenth)was applied in exploring the interaction between nefo-pam enantiomers and bovine serum albumin (BSA),mode of frontal analysis was selected to measure the binding constant,number of binding sites and the location of binding sites of BSA to both nefopam enantiomers.The opti-mal CEC conditions obtained were a running buffer consisted of 15 mmol /L ammonium acetate at pH 5.5,separa-tion voltage 5.0 kV,detection wavelength 215 nm,injection 10 kV ×6 s,solvent of samples consisted of 50 mmol/L ammonium acetate at pH 7.4.The results indicated that the monolith could provide a satisfactory resolution between the two enantiomers plateaus,BSA in the binding system didn′t disturb the separation or determination of nefopam enantiomers in electrochromatography.The frontal analysis demonstrated that BSA has only one binding site with both enantiomers,the binding constants (K)were 443 L/mol and 527 L/mol,respectively,and the dis-placement experiments indicated that binding site of both isomers to BSA molecule was the Sudlow siteⅡ.

Comparison of effects of intraoperative nefopam and ketamine infusion on managing postoperative pain after laparoscopic cholecystectomy administered remifentanil / 대한마취과학회지

BACKGROUND: Although intraoperative opioids provide more comfortable anesthesia and reduce the use of postoperative analgesics, it may cause opioid induced hyperalgesia (OIH). OIH is an increased pain response to opioids and it may be associated with N-methyl-D-aspartate (NMDA) receptor. This study aimed to determine whether intraoperative nefopam or ketamine, known being related on NMDA receptor, affects postoperative pain and OIH after continuous infusion of intraoperative remifentanil. METHODS: Fifty-four patients undergoing laparoscopic cholecystectomy were randomized into three groups. In the nefopam group (N group), patients received nefopam 0.3 mg/kg at the induction of anesthesia followed by a continuous infusion of 0.065 mg/kg/h. In the ketamine group (K group), patients received ketamine 0.3 mg/kg at the induction of anesthesia followed by a continuous infusion of 3 µg/kg/min. The control group did not received any other agents except for the standard anesthetic regimen. Postoperative pain score, first time and number of demanding rescue analgesia, OIH and degrees of drowsiness/sedation scale were examined. RESULTS: Co-administrated nefopam or ketamine significantly reduced the total amount of intraoperative remifentanil and postoperative supplemental morphine. Nefopam group showed superior property over control and ketamine group in the postoperative VAS score and recovery index (alertness and respiratory drive), respectively. Nefopam group showed lower morphine consumption than ketamine group, but not significant. CONCLUSIONS: Both nefopam and ketamine infusion may be useful in managing in postoperative pain control under concomitant infusion of remifentanil. However, nefopam may be preferred to ketamine in terms of sedation.

Nefopam Reduces Dysesthesia after Percutaneous Endoscopic Lumbar Discectomy

BACKGROUND: Neuropathic pain, including paresthesia/dysesthesia in the lower extremities, always develops and remains for at least one month, to variable degrees, after percutaneous endoscopic lumbar discectomy (PELD). The recently discovered dual analgesic mechanisms of action, similar to those of antidepressants and anticonvulsants, enable nefopam (NFP) to treat neuropathic pain. This study was performed to determine whether NFP might reduce the neuropathic pain component of postoperative pain. METHODS: Eighty patients, who underwent PELD due to herniated nucleus pulposus (HNP) at L4-L5, were randomly divided into two equal groups, one receiving NFP (with a mixture of morphine and ketorolac) and the other normal saline (NS) with the same mixture. The number of bolus infusions and the infused volume for 3 days were compared in both groups. The adverse reactions (ADRs) in both groups were recorded and compared. The neuropathic pain symptom inventory (NPSI) score was compared in both groups on postoperative days 1, 3, 7, 30, 60, and 90. RESULTS: The mean attempted number of bolus infusions, and effective infused bolus volume for 3 days was lower in the NFP group for 3 days. The most commonly reported ADRs were nausea, dizziness, and somnolence, in order of frequency in the NFP group. The median NPSI score, and all 5 median sub-scores in the NFP group, were significantly lower than that of the NS group until postoperative day 30. CONCLUSIONS: NFP significantly reduced the neuropathic pain component, including paresthesia/dysesthesia until 1 month after PELD. The common ADRs were nausea, dizziness, somnolence, and ataxia.

The Effect of Nefopam on Postoperative Fentanyl Consumption: A Randomized, Double-blind Study

BACKGROUND: Nefopam is a non-opioid, non-steroidal, centrally acting analgesic drug. The concomitant use of opioids and nefopam is believed to have many advantages over the administration of opioids alone for postoperative pain management. We conducted a randomized, double-blind study to determine the fentanyl-sparing effect of co-administration of nefopam with fentanyl for postoperative pain management via patient controlled analgesia (PCA). METHODS: Ninety female patients who underwent laparoscopic total hysterectomy under general anesthesia were randomized into 3 groups, Group A, fentanyl 1,000 µg; Group B, fentanyl 500 µg + nefopam 200 mg; and Group C, fentanyl 500 µg + nefopam 400 mg, in a total volume of 100 ml PCA to be administered over the first 48 h postoperatively without basal infusion. The primary outcome was total fentanyl consumption during 48 h; secondary outcomes included pain scores and incidence of side effects. RESULTS: Eighty-one patients were included in the analysis. The overall fentanyl-sparing effects of PCA with concomitant administration of nefopam during the first 48 h postoperatively were 54.5% in Group B and 48.9% group C. Fentanyl use was not significantly different between Groups B and C despite the difference in the nefopam dose. There were no differences among the three groups in terms of PCA-related side effects, although the overall sedation score of Group B was significantly lower than that of Group A. CONCLUSIONS: The concomitant administration of nefopam with fentanyl for postoperative pain management may allow reduction of fentanyl dose, thereby reducing the risk of opioid-related adverse effects.

Comparison of effect of electroacupuncture and nefopam for prevention of postanesthetic shivering in patients undergoing urologic operation under spinal anesthesia / 대한마취과학회지

BACKGROUND: Shivering during spinal anesthesia is a frequent complication and is induced by the core-to-peripheral redistribution of heat. Nefopam has minimal side effects and prevents shivering by reducing the shivering threshold. Electroacupuncture is known to prevent shivering by preserving the core body temperature. We compared the efficacies of electroacupuncture and nefopam for the prevention of shivering during spinal anesthesia. METHODS: Ninety patients scheduled for elective urological surgery under spinal anesthesia were enrolled in the study. Patients were randomly divided into the control group (Group C, n = 30), the electroacupuncture group (Group A, n = 30), and the nefopam group (Group N, n = 30). Groups C and A received 100 ml of isotonic saline intravenously for 30 minutes before spinal anesthesia, while Group N received nefopam (0.15 mg/kg) mixed in 100 ml of isotonic saline. Group A received 30 minutes of electroacupuncture before receiving anesthesia. Shivering scores, mean arterial pressure, heart rate, body temperature and side effects were recorded before, and at 5, 15, 30, and 60 minutes after spinal anesthesia. RESULTS: The incidence of postanesthetic shivering was significantly lower in Group N (10 of 30) and Group A (4 of 30) compared with that in Group C (18 of 30)(P < 0.017). Body temperature was higher in Group N and Group A than in Group C (P < 0.05). Hemodynamic parameters were not different among the groups. CONCLUSIONS: By maintaining body temperature during spinal anesthesia, electroacupuncture is as effective as nefopam in preventing postanesthetic shivering.

The Role of Spinal Dopaminergic Transmission in the Analgesic Effect of Nefopam on Rat Inflammatory Pain

BACKGROUND: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. METHODS: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. RESULTS: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. CONCLUSIONS: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.

Mechanical Antiallodynic Effect of Intrathecal Nefopam in a Rat Neuropathic Pain Model

Nefopam has a pharmacologic profile distinct from that of opioids or other anti-inflammatory drugs. Several recent studies demonstrate that nefopam has a mechanism of action similar to those of anti-depressants and anticonvulsants for treating neuropathic pain. The present study investigates the mechanical antiallodynic effect of nefopam using immunohistochemical study and western blot analysis in a rat neuropathic pain model. Twenty-eight male Sprague-Dawley rats were subjected to left fifth lumbar (L5) spinal nerve ligation and intrathecal catheter implantation, procedures which were not performed on the 7 male Sprague-Dawley rats in the sham surgery group (group S). Nefopam, either 10 or 100 microg/kg (group N10 or N100, respectively), and normal saline (group C) were intrathecally administered into the catheter every day for 14 days. The mechanical allodynic threshold of intrathecal nefopam was measured using a dynamic plantar aesthesiometer. Immunohistochemistry targeting cluster of differentiation molecule 11b (CD11b) and glial fibrillary acidic protein (GFAP) was performed on the harvested spinal cord at the level of L5. Extracellular signal-regulated kinase 1/2 (ERK 1/2) and cyclic adenosine monophosphate response element binding protein (CREB) were measured using western blot analysis. The N10 and N100 groups showed improved mechanical allodynic threshold, reduced CD11b and GFAP expression, and attenuated ERK 1/2 and CREB in the affected L5 spinal cord. In conclusion, intrathecal nefopam reduced mechanical allodynia in a rat neuropathic pain model. Its mechanical antiallodynic effect is associated with inhibition of glial activation and suppression of the transcription factors' mitogen-activated protein kinases in the spinal cord.

The analgesic effect of nefopam combined with low dose remifentanil in patients undergoing middle ear surgery under desflurane anesthesia: a randomized controlled trial / 대한마취과학회지

BACKGROUND: We investigated the effects of the combined administration of nefopam, a N-methyl-D-aspartate receptor antagonist and low dose remifentanil, on early postoperative pain and analgesic requirement. METHODS: Fifty patients scheduled to undergo mastoidectomy and tympanoplasty were randomized to be given either nefopam 40 mg mixed with normal saline 100 ml (Group N) or an equal amount of normal saline (Group C) before anesthesia induction. Anesthesia was maintained with 5-6 vol% desflurane and remifentanil 0.05-0.15 microg/kg/min during the surgery. Postoperative pain was controlled by titration of ketorolac in the postanesthesia care unit (PACU) and ward. We evaluated the intraoperative remifentanil dose, recovery profiles, ketorolac demand in the PACU and ward, numeric rating scale (NRS) for pain at time intervals of every 10 min for 1 h in the PACU, 6, 12, 18 and 24 h in a ward, as well as the time to first analgesic requirement in the PACU and ward. RESULTS: Ketorolac demand and NRS in the PACU were significantly lower in Group N than Group C (P = 0.002, P = 0.005, respectively). The time to first analgesic requirement in the PACU in Group N were significantly longer than Group C (P = 0.046). There were no significant differences in intraoperative remifentanil dose, ketorolac demand, NRS, and the time to first analgesic requirement in the ward between the groups. CONCLUSIONS: Nefopam administration combined with low dose remifentanil infusion reduces pain and analgesic consumption during the immediate postoperative period in patients undergoing middle ear surgery under desflurane anesthesia.

Effect of nefopam for patient-controlled analgesia after laparoscopic gastrectomy

BACKGROUND: Nefopam is a central acting, non-opioid analgesic used for control of postoperative pain. However, there are limited studies on the analgesic effect of nefopam for patient-controlled analgesia (PCA). We investigated the analgesic effect of nefopam mixed in fentanyl PCA following laparoscopic gastrectomy. METHODS: Sixty-six patients between the ages of 20 and 70 years, of American Society of Anesthesiologists physical status I, II or III, who were scheduled to undergo elective laparoscopic gastrectomy, were enrolled in the study. Patients were randomly assigned to the nefopam (N) or saline (S) group. Anesthesia was maintained with target controlled infusion of propofol and remifentanil. For PCA, patients in the N group received 100 mg nefopam and 30 microg/kg fentanyl. Patients in the S group received fentanyl 30 microg/kg. PCA infusion was started after 90 minutes from anesthesia induction. Pain by verbal rating scale at rest or on cough, shivering and postoperative nausea and vomiting were assessed immediately and after 30 minutes in the recovery room. Pain by verbal rating scale at rest or on cough, total volume of PCA, bolus button count, and additional analgesic requirements were assessed after 24 hour of PCA infusion. RESULTS: Shivering scores were statistically different between groups immediately and after 30 minutes in the recovery room. Pain by verbal rating scale at rest and additional analgesic requirements after 24 hour of PCA infusion were statistically different between groups. CONCLUSIONS: Addition of nefopam to patients on the fentanyl PCA regimen after laparoscopic gastrectomy resulted in effective postoperative pain control and reduced incidence of postoperative shivering.

Effects of Nefopam on Streptozotocin-Induced Diabetic Neuropathic Pain in Rats / 대한통증학회지

BACKGROUND: Nefopam is a centrally acting non-opioid analgesic agent. Its analgesic properties may be related to the inhibitions of monoamine reuptake and the N-methyl-D-aspartate (NMDA) receptor. The antinociceptive effect of nefopam has been shown in animal models of acute and chronic pain and in humans. However, the effect of nefopam on diabetic neuropathic pain is unclear. Therefore, we investigated the preventive effect of nefopam on diabetic neuropathic pain induced by streptozotocin (STZ) in rats. METHODS: Pretreatment with nefopam (30 mg/kg) was performed intraperitoneally 30 min prior to an intraperitoneal injection of STZ (60 mg/kg). Mechanical and cold allodynia were tested before, and 1 to 4 weeks after drug administration. Thermal hyperalgesia was also investigated. In addition, the transient receptor potential ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) expression levels in the dorsal root ganglion (DRG) were evaluated. RESULTS: Pretreatment with nefopam significantly inhibited STZ-induced mechanical and cold allodynia, but not thermal hyperalgesia. The STZ injection increased TRPM8, but not TRPA1, expression levels in DRG neurons. Pretreatment with nefopam decreased STZ-induced TRPM8 expression levels in the DRG. CONCLUSIONS: These results demonstrate that a nefopam pretreatment has strong antiallodynic effects on STZ-induced diabetic rats, which may be associated with TRPM8 located in the DRG.