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Transcutaneous electrical acupoint stimulation (TEAS) provides a convenient and standardized technique for pain treatment. The cold-pressor test is a simple and reliable model in humans for the induction of tonic pain. In this controlled study, the effects of TEAS on cold pressor-induced pain were evaluated in 22 healthy human subjects. Electrical stimulation at 4 Hz and 32 Hz was applied to He-Gu (LI 4) and Nui-Guan (P 6) acupoints for 15 minutes. Pain score ratings were evaluated at four time points from 30–170 seconds during the cold-pressor test. We observed an analgesic effect at both 4 Hz and 32 Hz of stimulation, and pain score rating reductions were statistically significant compared to control (p < 0.01). Our data support the efficacy of TEAS analgesia. However, there was no significant difference between pain scores at 4 Hz and 32 Hz stimulation.

It has been reported by Stein et al. that the immune system and peripheral opioid receptors are involved in the control of pain accompanying inflammation. Electroacupuncture (EA) is used to relieve various kinds of pain. However, little is known about the effect of electroacupuncture analgesia (EAA) during hyperalgesia elicited by inflammation. The aim of the present study was to compare (1) the individual variation of EAA, (2) the durability of EAA, and (3) the effect of naloxone on EAA between normal rats and rats subjected to acute inflammatory pain. Carrageenan was subcutaneously administered by intraplantar (i.pl.) injection of the left hind paw to induce a nociceptive response. Nociceptive thresholds were measured using the paw pressure threshold (PPT). Rats received EA at 3 Hz in the left anterior tibial muscles for 1 hour after carrageenan injection. Naloxone was administered by intraperitoneal (i.p.) or i.pl. injection just before EA. EAA was elicited in 15 of 29 normal rats. These rats were divided into responders and non-responders. EAA in the responder group was almost completely antagonized by i.p. injection of naloxone. In contrast, in all the rats with carrageenan-induced inflammation, EAA was elicited, lasted for at least 24 hours after carrageenan injection, and was dose-dependently antagonized by i.pl. injection, but not significantly by i.p. injection of naloxone. It seems likely that the EAA in the rats with carrageenan-induced inflammation differs from that in normal rats, and these findings suggest that peripheral opioid receptors are involved in EAA during inflammatory conditions.

Electroacupuncture (EA) is used to relieve various kinds of pain. However, the mechanistic basis of electroacupuncture analgesia (EAA) in inflammatory pain remains unclear. In the present study, we investigated whether endogenous peripheral corticotropin-releasing factor (CRF) or interleukin-1β (IL-1) participated in EAA during hyperalgesia elicited by carrageenan-induced inflammation. Carrageenan was subcutaneously administered by intraplantar (i.pl.) injection of the left hind paw to induce inflammation. Nociceptive thresholds were measured using the paw pressure threshold (PPT) (Randall Sellito Test). Rats received 3 Hz EA in the left anterior tibial muscles for 1 hour after carrageenan injection. The selective CRF antagonist, α-helical CRF, or the recombinant IL-1 receptor antagonist, IL-1ra, was administered by i.pl. injection of the inflamed paw or by intravenous (i.v.) injection 1 hour before EA. PPT decreased significantly 3 hours after carrageenan injection. This decrease persisted at least 24 hours after carrageenan injection. EA resulted in significant increases of PPT, moreover, PPT elevations lasted 24 hours after carrageenan injection. By contrast, PPT elevations produced by EA were dose-dependently antagonized by local i.pl. injection of α-helical CRF or IL-1ra. This PPT elevation was not influenced by i.v. injection of α-helical CRF or IL-1ra. These findings suggest that peripheral CRF or IL-1 participate in EAA during hyperalgesia. The release of CRF or IL-1 elicited by EA may trigger the release of opioid peptides within inflamed tissue which may activate peripheral opioid receptors and inhibit the pain.

The purpose of this study was to examine whether pain-induced brain activation was suppressed by acupuncture analgesia. We investigated the suppression of the pain-induced neuronal activation in specific brain areas of three male rhesus monkeys (aged four years old) using positron emission tomography (PET), in which changes in the regional cerebral blood flow (rCBF) were examined as an index of the neuronal activation. The brain areas such as the thalamus, insula and anterior cingulate cortex were activated by heating the tail of monkeys in 47°C water compared to the heating at 37°C. Those activations were suppressed by electroacupuncture (EA) with a 2 sec alteration of the frequency of 4 Hz/60 Hz at the right ST36 (the upper anterior tibial muscle) and the right LI4 (the back palm between the first and second metacarpal) acupoints. Meanwhile, this EA analgesic effect was confirmed by prolonging the tail withdrawal latencies from hot water in the temperature range from 45 to 50°C.These brain areas were corresponded to the pain-related areas as reported in previous studies. In conclusion, we were able to visualize the acupuncture analgesia in the CNS. We also detected the brain areas activated or inactivated by acupuncture. The areas that responded to acupuncture stimulation at 47°C water were different from the regions at 37°C. We consider that this difference in the response to acupuncture may support the variation of the clinical efficacy of acupuncture in patients bearing pain or other disorders.

The aim of the present study is to probe candidate genes which were involved in the electroacupuncture (EA) analgesia and to understand the molecular basis of the individual difference of EA analgesia in rats. We compared hypothalamus transcriptional profiles of responders with those of non-responders after 1 Hz EA treatment at ST36 acupoint for 1 hour by using oligonucleotide microarray. Responders and non-responders were determined by tail flick latency (TFL). A real-time quantitative RT-PCR was applied to validate the differential expressed genes. Our study provided a global hypothalamus transcriptional profile of EA analgesia in rats. We found that 63 and 3 genes were up- and down-regulated in the responder group, respectively. Half of the differentially expressed genes were classified into 9 functional groups which were ion transport, sensory perception, synaptogenesis and synaptic transmission, signal transduction, inflammatory response, apoptosis, transcription, protein amino acid phosphorylation and G-protein signaling. Glutamatergic receptors, ghrelin precursor, melanocortin 4 receptor (MC4-R) and neuroligin 1 were found to be up-regulated in the responder group which may become new targets for nociceptive study and deserve further investigation for developing new acupuncture therapy and intervention of pain modulation.

The present study was intended to examine the analgesic effect of the 70% methanol extract of Torenia concolor Lindley var. formosana Yamazaki (TC_MeOH) and betulin using models of acetic acid-induced writhing response and formalin test. In addition, we investigated the anti-inflammatory effect of TC_MeOH and betulin using model of λ-carrageenan-induced paw edema. We observed the activities of antioxidant enzymes (SOD, GPx and GR) in the liver and the levels of malondialdehyde (MDA) and nitric oxide (NO) in the edema paw. The results showed that TC_MeOH (1.0 and 2.0 g/kg) and betulin (30 and 90 mg/kg), significantly inhibited the acetic acid-induced writhing response. TC_MeOH (2.0 g/kg) and betulin (30 and 90 mg/kg) significantly inhibited formalin-induced licking time during both the early and late phases. TC_MeOH (0.5, 1.0 and 2.0 g/kg) and betulin (30 and 90 mg/kg) also significantly decreased the paw edema at the 4th hour after λ-carrageenan injection. Furthermore, TC_MeOH and betulin treatment also significantly increased the activities of SOD, GR and GPx in the liver while decreasing the level of MDA in the edema paw. Finally, betulin (30 and 90 mg/kg) also caused considerable reduction of NO level in the edema paw. Taken together, the present results indicated that TC_MeOH and betulin possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of TC_MeOH and betulin may be related to decreasing the levels of MDA and NO in the edema paw by increasing the activities of antioxidant enzymes in the liver.

Acupuncture treatment has been accepted worldwide. Many clinical trials have been conducted especially in analgesia. The present review includes almost all the important trials since 1970. Among all the pain conditions, postoperative pain, lower back pain, osteoarthritis of the knee and chronic headache are the most popular topics. We found that there are diverse conclusions in each condition; however, most trials agree that acupuncture is an effective therapeutic strategy for analgesia. As with regard to the placebo effect, there is no consensus. In chronic headache treatment, the placebo effect of acupuncture seems to be large. However, in osteoarthritis, the placebo effect is minimal. Another issue is the non-specific physiologic response to piercing the skin. We believe that this effect produces analgesia in some heterogeneous syndrome such as lower back pain. However, this effect is not superior to the specific therapeutic effect of acupuncture based on TCM theory in all the pain conditions reviewed here. We also notice that the design of the sham acupuncture or the placebo has great impact on the result. Rigorous design can minimize the non-specific and placebo effects of acupuncture. Therefore, the real effect of acupuncture can be investigated well. We conclude that acupuncture is a proven treatment for relieving pain. This conclusion is based on specific effects of acupuncture rather than placebo.

In this study, we evaluated the analgesic effect of methanol extract from Desmodium triflorum DC (MDT) by using animal models of acetic acid-induced writhing response and formalin test. The anti-inflammatory effect of MDT was investigated by λ-carrageenan-induced paw edema in mice. In order to study the anti-inflammatory mechanism of MDT, we detected the activities of glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver, the levels of interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), malondialdehyde (MDA) and nitric oxide (NO) in the edema paw tissue. In the analgesic test, MDT (0.5 and 1.0 g/kg) decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test. In the anti-inflammatory test, MDT (0.5 and 1.0 g/kg) decreased the paw edema at the 3rd, 4th, 5th and 6th hour after λ-carrageenan administration. On the other hand, MDT increased the activities of SOD and GRd in liver tissues and decreased the MDA level in the edema paw at the 3rd hour after λ-carrageenan-induced inflammation. MDT also affected the levels of interleukin-1β, tumor necrosis factor-α, NO and MDA which were induced by λ-carrageenan. The results suggested that MDT possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of MDT might be related to the decreases in the level of MDA in the edema paw via increasing the activities of SOD and GRd in the liver, and the NO level via regulating the IL-1β production and the level of TNF-α in the inflamed tissues.

In this study, we evaluated the analgesic effect of the methanol extract of Kalanchoe gracilis (MKGS) stem in animal models by inducing writhing response with acetic acid and conducting formalin test. The anti-inflammatory effect of MKGS was also estimated on mice with λ-carrageenan induced paw edema model. In order to investigate the anti-inflammatory mechanism of MKGS, we analyzed the activities of glutathione peroxidase (GPx) and glutathione reductase (GRx) in the liver, and the levels of interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), malondialdehyde (MDA) and nitric oxide (NO) in the edema paw tissue. In the analgesic tests, MKGS (0.5 and 1.0 g/kg) decreased both the acetic acid-induced writhing response and the licking time in the late phase of the formalin test. In the anti-inflammatory test, MKGS (0.1, 0.5 and 1.0 g/kg) decreased paw edema at the third, fourth, fifth and sixth hours after λ-carrageenan had been administrated. Furthermore, MKGS increased the activities of SOD and GRx in liver tissues and decreased MDA level in the edema paws three hours after λ-carrageenan was injected. MKGS also affected the levels of IL-1β, TNF-α and NO induced by λ-carrageenan. All these results suggested that MKGS possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of MKGS might be related to the lowering of MDA level in the edema paw via increasing the activities of superoxide dismutase (SOD) and GRx in the liver, as well as the decreases in the levels of TNF-α and NO, and the production of IL-1β in inflamed tissues.

I-Tiao-Gung has long been used in the Kinmen area of Taiwan as an anti-inflammatory agent for the treatment of rheumatic illness. The roots of Flemingia lineata (FL), Flemingia macrophylla (FM) and Flemingia prostrata (FP) are also used as I-Tiao-Gung in the Taiwan markets. In the present study, we investigated the analgesic effect of aqueous extracts of Flemingia lineata (FL), Flemingia macrophylla (FM), and Flemingia prostrata (FP) by acetic acid-induced writhing response, formalin test, and the anti-inflammatory effect of FM, FL and FP by λ-carrageenan-induced paw edema in mice. We also detected the changes in the activities of superoxide dismutase (SOD), glutathione reductase (GRx) and glutathione peroxidase (GPx) of liver in the λ-carrageenan-induced paw edema in mice to investigate the anti-inflammatory mechanism of FL and FM.

The results showed that FL and FM significantly inhibited the acetic acid-induced writhing response and formalin-induced licking time during the late phase (p < 0.001). FL and FM also significantly decreased the λ-carrageenan-induced paw edema (p < 0.001). FL and FM significantly increased the GRx and GPx activities in the liver and decreased the levels of malondialdehyde (MDA) and nitric oxide (NO) in the edema paw (p < 0.001).

These results indicated that FL and FM possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of FL and FM might be related to the decrease in the level of MDA in the edema paw via increasing the activities of GPx and GRx in the liver and decreasing the NO level in the edema paw.

Rhizoma Arisaematis (RA, the rhizome of Pinellia pedatisecta Schott) is a traditional Chinese medicine commonly used in the treatment of convulsions, inflammation, and cancer. Despite the fact that it has been used for more than 2000 years, the pharmacological and toxic effects of traditionally processed products of RA are still unclear. In this study, we attempted to investigate the effects exerted by untreated crude RA and different preparations of RA treated with alumen in combination with ginger juice (Zhinanxing) or bile juice (Dannanxing) in ICR mice. The results showed that both the Zhinanxing and Dannanxing water extracts exerted significantly increased sedative effects, as indicated by the inhibitory effects on ambulatory distances, jumps, vertical-plane entries, and prolonged pentobarbital-induced sleeping time. The extracts also exerted significantly increased analgesic effects (increase of tail flick latency in nociceptive testing) in mice than did the unprocessed crude RA after oral administration for one to three days, and effects persisted 18 days after the cessation of treatment. By contrast, the toxic effects, such as an increase in stereotype-1 episodes of locomotor activities and reduction of the retention time on a rotating rod (motor equilibrium dysfunction), were observed only in mice treated with the unprocessed crude RA for three consecutive days, and effects persisted for 18 days after the cessation of treatment. These neurotoxic effects were accompanied by an increase in plasma lipid peroxidation (LPO), decrease in whole blood nitric oxide (NO_x) levels, and inhibition of Na⁺/K⁺-ATPase activities in membrane fractions of erythrocytes and in the cerebral cortex. In conclusion, these findings provide scientific evidence that the processed RA indeed possesses not only enhanced neuropharmacological efficacy but also reduced neurotoxic effects as compared to the unprocessed crude RA. The signaling of NO_x/oxidative stress/Na⁺-K⁺- ATPase activities played a role, at least in part, in the underlying mechanisms of neurotoxic effects induced by the crude RA.

We investigated possible mechanisms of analgesic and anti-inflammatory activities of the methanol extract from the leaf of Elaeagnus oldhamii Maxim. (EO_MeOH). EO_MeOH was evaluated for its analgesic activity in acetic acid-induced writhing response and formalin test, and anti-inflammatory effect was examined by λ-carrageenan-induced paw edema assay. We detected the activities of GPx, GRd and SOD in the liver, and the levels of inflammatory mediators including IL-1β, IL-6, TNF-α, COX-2, MDA and NO in the edema paw to investigate the mechanism of action against inflammation. Total polyphenol, flavonoid and flavanol contents of EO_MeOH were detected to explore its antioxidant activities. Results showed that, in the analgesic test, EO_MeOH decreased acetic acid-induced writhing response and the licking time in the late phase of formalin test. In the anti-inflammatory test, EO_MeOH decreased paw edema at the 2nd, 3rd, 4th and 5th h after λ-carrageenan had been injected. EO_MeOH increased the activities of SOD and GPx in liver tissue and decreased MDA, NO, IL-1β, IL-6, TNF-α and COX-2 levels in paw edema tissue at the 3rd h after λ-carrageenan-induced inflammatory reaction. EO_MeOH exhibited abundant polyphenol, flavonoid and flavanol contents. In HPLC fingerprint test of EO_MeOH, two index ingredients, ursolic acid and pomolic acid, were isolated from EO_MeOH and were exhibited in HPLC chromatographic analysis. The results demonstrated analgesic and anti-inflammatory effects of EO_MeOH. It was indicated that the anti-inflammatory mechanism of EO_MeOH may be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx and GRd in the liver. Additionally, EO_MeOH decreased IL-1β, IL-6, TNF-α and COX-2 levels in the edema paw. The results suggested its value in future development of herbal medicine for the treatment of inflammatory diseases.

The seeds of Cuscuta chinensis, Cuscutae Semen, are commonly used as a medicinal material for treating the aching and weakness of the loins and knees, tonifying the defects of the liver and the kidney, and treating the diarrhea due to hypofunction of the kidney and the spleen. Since aching and inflammation are highly correlated with such diseases, the aim of this study is to investigate the possible antinociceptive and anti-inflammatory mechanisms of the seeds of C. chinensis. The antinociceptive effect of the seeds of C. chinensis was evaluated via the acetic acid-induced writhing response and formalin-induced paw licking methods. The anti-inflammatory effect was evaluated via the λ-carrageenan induced mouse paw edema method. The results found that 100 and 500 mg/kg of the methanol extract of the seeds of C. chinensis(CC_MeOH) significantly decreased (p < 0.01 and p < 0.001, respectively) the writhing response in the acetic acid assay. Additionally, 20–500 mg/kg of CC_MeOH significantly decreased licking time at the early (20 and 100 mg/kg, p < 0.001) and late phases (100 mg/kg, p < 0.01; 500 mg/kg, p < 0.001) of the formalin test, respectively. Furthermore, CC_MeOH (100 and 500 mg/kg) significantly decreased (p < 0.01 and p < 0.001, respectively) edema paw volume four hours after λ-carrageenan had been injected. The results in the following study also revealed that the anti-inflammatory mechanism of CC_MeOH may be due to declined levels of NO and MDA in the edema paw by increasing the activities of SOD, GPx and GRd in the liver. In addition, CC_MeOH also decreased IL-1β, IL-6, NF-κB, TNF-α, and COX-2 levels. This is the first study to demonstrate the possible mechanisms for the antinociceptive and anti-inflammatory effects of CC_MeOHin vivo. Thus, it provides evidence for the treatment of Cuscutae Semen in inflammatory diseases.

This study investigated the influence of the histamine H₁ receptor antagonists, chlorpheniramine (CHL) and pyrilamine, on the analgesic effects of acupuncture in mice. Nociceptive response was evaluated by the acetic acid-induced abdominal writhe test. Electroacupuncture (EA) at bilateral ST36 reduced the manifestations of acetic acid-induced abdominal writhing, whereas needle insertion without electrostimulation had no such effect. Notably, EA treatment was not associated with any analgesic effects in mice pretreated with naloxone. Low doses of CHL (0.6mg/kg; p.o.) or pyrilamine (2.5mg/kg; i.p.) as monotherapy did not affect acetic acid-induced abdominal writhing. However, when each agent was combined with EA, acetic acid-induced abdominal writhing was reduced by a greater extent when compared with EA alone. Interestingly, the effects of CHL on acupuncture analgesia were not completely reversed by naloxone treatment. Acetic acid induced increases of phospho-p38 expression in spinal cord, as determined by immunofluorescence staining and Western blot analysis. These effects were attenuated by EA at ST36 and by low doses of histamine H₁ receptor antagonists, alone or in combination. Our findings show that relatively low doses of histamine H₁ receptor antagonists facilitate EA analgesia via non-opioid receptors. These results suggest a useful strategy for increasing the efficacy of EA analgesia in a clinical situation.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory and debilitating disease that involves the systemic imbalance of the immune network. Previous studies have shown that acupuncture can help treat RA. However, its specific mechanisms are not fully understood. Thus, the present study was designed to clarify the mechanisms of acupuncture acted on RA via immune network modulation using complete Freund’s adjuvant (CFA)-induced arthritic rats. Results revealed that manual acupuncture (MA) could alleviate the inflammation and pain of infected joints. Moreover, MA could effectively stimulate the innate immune cytokines (IL-1$\alpha$, IL-1$\beta$, IL-6, IL-7, IL-18, TNF-$\alpha$) and adaptive immunity cytokines (IL-2, IL-12, IFN-$\gamma$, IL-4, IL-5, IL-10, IL-13, IL-17) as the main part of the immune response and repaired damage of RA. These complex immunomodulatory processes were analyzed quantitatively by cell–cell communication (CCC) networks. The CCC networks demonstrated that the immune networks were enhanced with the development of RA, while MA enhanced the immune networks in the early stage to act on RA and promoted the immune-network to a normal level at the late stage. Moreover, we found that monocyte/macrophage and endothelial cells were the key cells of innate immunity and body cells; T_H1, T_H2 and B cells were the key cells of adaptive immunity, which were also the main target cells for MA regulation.

Pain is a widespread and complex symptom which causes serious emotional and social burdens to individuals and society. Most patients with pain rely heavily on over the counter (OTC) and prescription pain killers. However, there would be a number of issues that arise from the use of pain killers, in which safety and addiction are the most critical issues. For traditional Chinese medicine (TCM), pain is a result of the meridians being blocked. This could occur as a symptom of or be caused by various diseases. In this case, the key to relieve pain depends on dredging the meridian or meridians. Acupuncture has been practiced in China for over 2000 years to lessen pain. It is based on the “meridian theory”. Acupuncture is being used more widely and with a growing number of people in the treatment of pain because it is safer and has fewer side effects. Along with growing use and interest in acupuncture to treat pain, more attention has been paid to the mechanism underlying its analgesic effect, which is mainly associated with the changes of neurotransmitters. In this review, we summarize and analyze the range and mechanism of acupuncture analgesia treatment.

The development of effective drug-loaded dressings has been considered a hot research topic for biomedical therapeutics, including the use of botanical compounds. For wound healing, adequate dressings can provide a good microenvironment for drug release, such as lidocaine. Biological macromolecular materials such as alginate show excellent properties in wound management. This study involves the preparation and evaluation of biocompatible multilayered-structure microspheres composed of chitosan, porous gelatin, and calcium alginate microspheres. The multilayered structure microspheres were named chitosan@ porous gelatin@ calcium alginate microspheres (CPAMs) and the drugs were rapidly released by the volume expansion of the calcium alginate microspheres. The in vitro release curve revealed that the peak release of lidocaine from CPAMs was reached within 18min. After 21min, the remaining lidocaine was then slowly released, and the active drug release was converted to a passive drug release phase. The initial release effect of lidocaine was much better than that reported in the published studies. Additionally, blood coagulation experiments showed that CPAMs coagulated blood in 60s, and the blood liquidity of the CPAMs group was worse than that of the woundplast group. Therefore, the coagulation characteristics of CPAMs were superior to the commonly used woundplast containing lidocaine healing gel. These study outcomes indicated that the CPAMs acted as fast-release dressings for faster pain control and better coagulation properties.

We studied the use of a continuous peripheral nerve block (CPNB) in the distal forearm and wrist immediately after emergent surgery for severe hand trauma in 22 hands. After emergent surgery, a 2–3 cm longitudinal incision was made at the distal forearm and an 18-gauge catheter was inserted along the peripheral nerves. All patients received postoperative analgesia by continuous infusion of 0.2% ropivacaine at 2 ml/h for seven to 21 days. Pain score remained low during postoperative period and only a small number of analgesic rescues were needed. There were no major complications related to the CPNB and one patient showed mild superficial infection at the insertion site that immediately recovered after catheter removal. This method provides good postoperative analgesia without loss of motor function in extrinsic hand muscles and should be considered as a postoperative pain management for severe hand trauma.

Purpose: Pregabalin is a new neuropathic drug that gained recent popularity in treatment of acute postoperative pain. The purpose of this study is to study the effect of pregabalin in pain management in the first 24 h after total knee arthroplasty. Methods: PubMed, Scopus, EBSCO, and Web of science were searched for randomized controlled trials that study the effect of pregabalin in the management of pain after total knee arthroplasty. Pain scores at rest and with movement and opioid consumption in the first 24 h and the occurrence of adverse events were the primary outcome measure. The statistical software RevMan 5.3 was used to analyze the statistical significance of the results. Results: A total of 5 randomized controlled trials with 608 were collected. There was no significant benefit from the use of pregabalin in the management of pain in the perioperative period in patients undergoing primary total knee arthroplasty. Pain score after 24h at rest using 150 mg/day was (MD $-$0.53, P value 0.23). Pain score after 24 h with movement using doses less than 300 mg/day was (MD $-$1.11, P value 0.79). Opioid intake was not significantly reduced in patient taking pregabalin using doses less than 300 mg/day or doses higher than 300 mg/day (SMD $-$0.42, 0.59. P value 0.10, 0.42, respectively). Most of studies observed increased occurrence of adverse events with the use of pregabalin. Conclusion: This study demonstrates that pregabalin does not decrease pain scores in the first 24 h after total knee arthroplasty while it increases the occurrence of side effects.

Purpose: Evaluate the reliability of the early functional recovery and postoperative pain control using adductor canal block (ACB) compared with that using femoral nerve block (FNB) in patients undergoing total knee replacement (TKR). Patients and Methods: A total of 80 patients scheduled for TKR were randomly and blindly distributed into two groups (40 patients each). Group A received ACB and group F received FNB. The early quadriceps strength, range of motion and pain control were assessed after surgery during the first 48h. Results: Patients in group F had significantly less quadriceps power postoperatively than those in group A. There were no significant differences between the two studied groups as regard ambulation, range of motion and pain estimation. Conclusion: Since both blocks have comparable analgesic effect and opioid consumption rates, the increased quadriceps muscle strength and ability to ambulate on the first postoperative day is the driving factor in selecting the ACB. With the findings discussed in our study and in literature, an ACB is a viable option in place of a FNB in patients undergoing a total knee arthroplasty. Additional large participant randomized controlled studies should be conducted to further discover the benefits of an ACB in patients undergoing a total knee arthroplasty.