Dermorphin [D-Arg2, Lys4] (1-4) Amide Alleviates Frostbite-Induced Pain by Regulating TRP Channel-Mediated Microglial Activation and Neuroinflammation.

Cold injury or frostbite is a common medical condition that causes serious clinical complications including sensory abnormalities and chronic pain ultimately affecting overall well-being. Opioids are the first-choice drug for the treatment of frostbite-induced chronic pain; however, their notable side effects, including sedation, motor incoordination, respiratory depression, and drug addiction, present substantial obstacle to their clinical utility. To address this challenge, we have exploited peripheral mu-opioid receptors as potential target for the treatment of frostbite-induced chronic pain. In this study, we investigated the effect of dermorphin [D-Arg2, Lys4] (1-4) amide (DALDA), a peripheral mu-opioid receptor agonist, on frostbite injury and hypersensitivity induced by deep freeze magnet exposure in rats. Animals with frostbite injury displayed significant hypersensitivity to mechanical, thermal, and cold stimuli which was significant ameliorated on treatment with different doses of DALDA (1, 3, and 10 mg/kg) and ibuprofen (100 mg/kg). Further, molecular biology investigations unveiled heightened oxido-nitrosative stress, coupled with a notable upregulation in the expression of TRP channels (TRPA1, TRPV1, and TRPM8), glial cell activation, and neuroinflammation (TNF-α, IL-1ß) in the sciatic nerve, dorsal root ganglion (DRG), and spinal cord of frostbite-injured rats. Treatment with DALDA leads to substantial reduction in TRP channels, microglial activation, and suppression of the inflammatory cascade in the ipsilateral L4-L5 DRG and spinal cord of rats. Overall, findings from the present study suggest that activation of peripheral mu-opioid receptors mitigates chronic pain in rats by modulating the expression of TRP channels and suppressing glial cell activation and neuroinflammation.

Peripheral morphine reduces acute pain in inflamed tissue after third molar extraction: A double-blind, randomized, active-controlled clinical trial.

BACKGROUND: The clinical use of peripheral analgesic effects of opioids has been investigated in numerous controlled clinical trials. The majorities of these have tested the local, intra-articular administration of morphine in knee surgery and have demonstrated marginal postoperative analgesia. OBJECTIVE: We examined direct morphine infiltration of the surgical site in a clinical model of tooth pain under two different conditions. Eighty-eight patients undergoing surgical tooth removal entered into the two prospective, parallel, randomized, double-blind studies. METHODS: Patients undergoing surgical tooth removal received a standard local anaesthetic solution (articaine plus epinephrine) before surgery. Patients were assigned to an injection of peripheral 2mg morphine either into non-inflamed (Trial I) or inflamed (Trial II) submucous tissue before the surgery. Patients who received an intramuscular morphine in the upper arm were concomitantly given 1ml isotonic saline (NaCl) as a submucous injection. Patients who received a submucous injection of morphine peripherally were concomitantly given an intramuscular injection (IM) of 1ml of NaCl in the upper arm. Postoperative pain intensity was assessed by the numeric rating scale every 30min for the first 2h and then every hour for the next 8h after surgery. In addition, patients recorded the occurrence of side effects and the supplemental consumption of ibuprophen and codeine+paracetamol combination tablets. RESULTS: Of the eighty-eight original participants, nine patients (4 patients in Trial I and 5 patients in Trial II) were withdrawn for protocol noncompliance and loss at follow-up. Thirty-one patients in trial I and forty-eight patients in trial II were analyzed. Patients receiving 2mg morphine into non-inflamed tissue did not show any further reduction in pain scores and pain medication consumption compared to IM morphine group (Trial I). In patients receiving 2mg morphine into inflamed tissue, pain scores at rest were reduced to a similar extent in both groups at all measurement times up to 10h in the follow-up (Trial II). At the same time, in the area under the curves pain scores on swallowing between 2 and 6h in the peripheral morphine group (5.2±5.6) were significantly lower than in the IM morphine group (9.3±7.3, p=0.03), demonstrating the marginal analgesic efficacy of additional morphine. Sedation scores were significantly higher in the peripheral morphine group only 1h after surgery in Trial I (p=0.008). The time to first analgesic intake was similar between groups. No serious side effects were reported. CONCLUSIONS: Our results showed in patients undergoing surgical tooth removal that injection of 2mg of morphine into inflamed tissue results in significantly lower pain scores on swallowing in the early postoperative state while administration into non-inflamed tissue is not effective. IMPLICATIONS: Our studies indicate that the peripheral administration of opioids, at the doses and conditions set out for these two studies, produces significant analgesia by a pharmacologically specific mechanism that is active in chronically, but not acutely, inflamed tissue. Thus, consistent with preclinical experimental studies, the requirement of an inflammatory process for the occurrence of the peripheral opioid effects is also found in the clinical setting.

Analgesia posquirúrgica con bupivacaína y morfina en cirugía de hombro mediante catéter intrarticular / Postoperative analgesia with bupivacaine and morphine through an intra-articular catheter in shoulder surgery

Introducción: la cirugía descompresiva en el síndrome doloroso de hombro es relativamente frecuente. El dolor posquirúrgico dificulta la rehabilitación temprana de estos pacientes y su reincorporación social y laboral. Objetivo: evaluar y demostrar la eficacia del uso de la combinación de bupivacaína-morfina vs. bupivacaína sola, administradas a través de catéter intrarticular para la analgesia y rehabilitación posoperatoria en cirugía de hombro. Métodos: se realizó un estudio longitudinal prospectivo y analítico a 80 pacientes entre 40 y 65 años de edad, de ambos sexos, atendidos en el Hospital Militar Central "Dr. Luis Díaz Soto" de La Habana, que comprendió los meses desde octubre de 2009 hasta mayo de 2010. Los pacientes se dividieron al azar en 2 grupos de 40 individuos cada uno. Al Grupo I se le añadió al anestésico local, 2 mg de morfina liofilizada cada 24 horas. Al Grupo II solo bupivacaína al 0,25 % (20 mL) cada 6 horas. Se evaluó analgesia posoperatoria según la Escala Visual Análoga (EVA). Se compararon los resultados mediante prueba de Chicuadradocon un grado de confiabilidad de 95 %. Resultados: la prolongación de la analgesia posoperatoria combinada en el Grupo I fue de un promedio de 13,5 horas vs. 4,55 horas en el Grupo II donde se usó solo bupivacaína durante las primeras 24 horas; y se notó igualmente una mejor evolución del dolor en las siguientes 24 a 48 horas para el Grupo I. Conclusiones: la utilización de la mezcla anestésica con el analgésico, para aliviar el dolor posoperatorio mediante catéter intrarticular en cirugía de hombro, es más eficaz, con leves efectos colaterales de fácil manejo, lo que permite una rehabilitación precoz.

Introduction: decompressive surgery is relatively common in shoulder pain syndrome. Postsurgical pain hampers the early rehabilitation of these patients and their reincorporation to work and social life. Objective: dvaluate and demonstrate the efficacy of the use of the bupivacaine-morphine combination vs. bupivacaine alone, administered through an intra-articular catheter, for postoperative analgesia and rehabilitation in shoulder surgery. Methods: an analytical prospective longitudinal study was conducted with 80 patients of both sexes aged 40-65 cared for at "Dr. Luis Diaz Soto" Central Military Hospital in Havana, which extended from October 2009 to May 2010. The patients were randomly distributed into 2 groups, each with 40 members. In Group I, 2 mg of lyophilized morphine were added to the local anesthetic every 24 hours. In Group II, only 0.25 % bupivacaine (20 mL) was added every 6 hours. Postoperative analgesia was evaluated with the Analog Visual Scale (AVS). Results were compared by means of a chi-square test with a 95 % confidence degree. Results: on average, prolongation of combined postoperative analgesia in Group I was 13.5 hours vs. 4.55 hours in Group II, where only bupivacaine was used during the first 24 hours. A better evolution of pain was also observed in Group I during the next 24 to 48 hours. Conclusions: Administration of the anesthetic mixture combined with the analgesic through an intra-articular catheter to relieve postoperative pain in shoulder surgery is more effective, with mild, easily manageable side effects, thus enabling early rehabilitation.

Analgesia posquirúrgica con bupivacaína y morfina en cirugía de hombro mediante catéter intrarticular / Postoperative analgesia with bupivacaine and morphine through an intra-articular catheter in shoulder surgery

Introducción: la cirugía descompresiva en el síndrome doloroso de hombro es relativamente frecuente. El dolor posquirúrgico dificulta la rehabilitación temprana de estos pacientes y su reincorporación social y laboral. Objetivo: evaluar y demostrar la eficacia del uso de la combinación de bupivacaína-morfina vs. bupivacaína sola, administradas a través de catéter intrarticular para la analgesia y rehabilitación posoperatoria en cirugía de hombro. Métodos: se realizó un estudio longitudinal prospectivo y analítico a 80 pacientes entre 40 y 65 años de edad, de ambos sexos, atendidos en el Hospital Militar Central Dr. Luis Díaz Soto de La Habana, que comprendió los meses desde octubre de 2009 hasta mayo de 2010. Los pacientes se dividieron al azar en 2 grupos de 40 individuos cada uno. Al Grupo I se le añadió al anestésico local, 2 mg de morfina liofilizada cada 24 horas. Al Grupo II solo bupivacaína al 0,25 por ciento (20 mL) cada 6 horas. Se evaluó analgesia posoperatoria según la Escala Visual Análoga (EVA). Se compararon los resultados mediante prueba de Chi cuadrado con un grado de confiabilidad de 95 por ciento. Resultados: la prolongación de la analgesia posoperatoria combinada en el Grupo I fue de un promedio de 13,5 horas vs. 4,55 horas en el Grupo II donde se usó solo bupivacaína durante las primeras 24 horas; y se notó igualmente una mejor evolución del dolor en las siguientes 24 a 48 horas para el Grupo I. Conclusiones: la utilización de la mezcla anestésica con el analgésico, para aliviar el dolor posoperatorio mediante catéter intrarticular en cirugía de hombro, es más eficaz, con leves efectos colaterales de fácil manejo, lo que permite una rehabilitación precoz(AU)

Introduction: decompressive surgery is relatively common in shoulder pain syndrome. Postsurgical pain hampers the early rehabilitation of these patients and their reincorporation to work and social life. Objective: dvaluate and demonstrate the efficacy of the use of the bupivacaine-morphine combination vs. bupivacaine alone, administered through an intra-articular catheter, for postoperative analgesia and rehabilitation in shoulder surgery. Methods: an analytical prospective longitudinal study was conducted with 80 patients of both sexes aged 40-65 cared for at Dr. Luis Diaz Soto Central Military Hospital in Havana, which extended from October 2009 to May 2010. The patients were randomly distributed into 2 groups, each with 40 members. In Group I, 2 mg of lyophilized morphine were added to the local anesthetic every 24 hours. In Group II, only 0.25 percent bupivacaine (20 mL) was added every 6 hours. Postoperative analgesia was evaluated with the Analog Visual Scale (AVS). Results were compared by means of a chi-square test with a 95 percent confidence degree. Results: on average, prolongation of combined postoperative analgesia in Group I was 13.5 hours vs. 4.55 hours in Group II, where only bupivacaine was used during the first 24 hours. A better evolution of pain was also observed in Group I during the next 24 to 48 hours. Conclusions: Administration of the anesthetic mixture combined with the analgesic through an intra-articular catheter to relieve postoperative pain in shoulder surgery is more effective, with mild, easily manageable side effects, thus enabling early rehabilitation(AU)

Fentanyl supplement expedites the onset time of sensory and motor blocking in interscalene lidocaine anesthesia.

BACKGROUND AND THE PURPOSE OF THE STUDY: Opioids are usually used in regional anesthesia, with or without local anesthetics to improve the regional block or postoperative pain control. Since no data are available on fentanyl's effect on the onset time of lidocaine interscalene anesthesia, the purpose of this study was to examine its effect on the onset time of sensory and motor blockade during interscalene anesthesia. METHODS: In a prospective, randomized, double-blind study, ninety patients scheduled for elective shoulder, arm and forearm surgeries under an interscalene brachial plexus block.They were randomly allocated to receive either 30 ml of 1.5% lidocaine with 1.5 ml of isotonic saline (control group, n=39) or 30 ml of 1.5% lidocaine with 1.5 ml (75 µg) of fentanyl (fentanyl group, n=41). Then the onset time of sensory and motor blockades of the shoulder, arm and forearm were evaluated every 60 sec. The onset time of the sensory and motor blockades was defined as the time between the last injection and the total abolition of the pinprick response and complete paralysis. The duration of sensory blocks were considered as the time interval between the administration of the local anesthetic and the first postoperative pain sensation. RESULTS: Ten patients were excluded because of unsuccessful blockade or unbearable pain during the surgery. The onset time of the sensory block was significantly faster in the fentanyl group (186.54±62.71sec) compared with the control group (289.51±81.22, P<0.01). The onset times of the motor block up to complete paralysis in forearm flexion was significantly faster in the fentanyl group (260.61±119.91sec) than the control group (367.08±162.43sec, P<0.01). There was no difference in the duration of the sensory block between two groups. CONCLUSION: Results of the study showed that the combination of 75 µg fentanyl and 1.5% lidocaine solution accelerated the onset of sensory and motor blockade during interscalene anesthesia.