Comparison of Painful Response to Mechanical Stimulation of the Plantar and Dorsal Surface of Paw Following Chronic Constriction Injury-induced Neuropathic Pain

Mechanical and thermal stimuli were used to evaluate neuropathic pain-like behavior in animal models usually. Mechanical stimulation of paw plantar surface is commonly used to determine mechanical allodynia. In the present study, paw withdrawal response to plantar surface stimulation was compared with paw withdrawal response to dorsal surface stimulation. To this end, a total of 30 female Wistar rats (180-220 g), were assigned randomly to three groups as intact (without any manipulation), sham (incision of skin and muscles without nerve injury), and neuropathy (sciatic nerve lesion) with 10 in each group. To induction of neuropathy (chronic constriction injury), four movable ligations were established around the sciatic nerve using catgut chromic suture with a distance of one millimeter apart and then wound incision was closed. In the sham group, the incision site was closed without nerve ligation. Mechanical allodynia was examined by Von Frey filaments for four weeks. The findings indicated that the paw withdrawal threshold following dorsal surface stimulation was significantly reduced compared to the sham group at day 21 post-surgery. Moreover, paw withdrawal threshold following plantar surface stimulation significantly decreased compared to the sham group at day 21 post-surgery. The present results regarding the sham group showed that the paw withdrawal threshold after mechanical stimulation of the plantar surface was not significantly different from that of the dorsal surface paw. In addition, and there was no significant difference between the paw withdrawal response to plantar surface and dorsal one. In conclusion, paw withdrawal threshold to plantar surface mechanical stimulation was not significantly different from one in dorsal surface following neuropathic pain induced by chronic constriction injury.

Critical interactions between opioid and cannabinoid receptors during tolerance and physical dependence development to opioids in the murine gastrointestinal tract: proof of concept

Introduction Tolerance (TOL) and physical dependence (PD) constitute important limitations of opioid therapy. The aim of our study was to validate research tools to investigate TOL and PD and to characterize the interactions between opioid (OR) and cannabinoid (CB) receptors in these processes in the GI tract. Methods TOL was assessed through the comparison of morphine ability to inhibit electrically evoked smooth muscles contractility in the mouse ileum that was previously incubated with/without morphine for 1 h. To evaluate the PD, the ileum was incubated with morphine for 10 min, then challenged with naloxone to induce withdrawal response (WR). The OR/CB interactions were evaluated using mixed agonist (PR-38) and AM-251 (CB1 antagonist). Results The inhibitory effect of morphine on ileal contractions was weaker in tissue incubated with this opioid than in tissue incubated without opioid. The opposite was noted for PR-38. In tissues exposed to morphine, but not to PR-38, naloxone induced a WR. The blockage of CB1 receptors with AM-251 before the addition of PR-38 resulted in a naloxone-induced WR. Conclusion The co-activation of OR and CB reduced development of TOL and PD to opioids in the mouse GI tract and mixed OR/CB agonists are promising alternative to currently used opioid drugs.

Effects of COX 1-2 Inhibitors on Prevention of Rocuronium Injection Pain: Controlled, Randomised, Double Blind Study

Purpose : Rocuronium bromide is a painful agent while general anesthesia induction. The aim of the study is to investigate the effects of cox inhibitors as a resque agent against the rocuronium pain Methodology : Sixty patients enrolled for the general anesthesia enrolled in this study. Patients were allocated into two groups (Group 1: Dexkethoprofen group, Group 2: Control group) .Pain was evaluated by during rocuronium injection, patients were scored by a scale showed below. 0;No movement response to injection 1;Mild movement response to injection 2;Hand withdrawal response to injection 3;Arm withdrawal response to injection We also evaluated the pain with 2 questions when the patient was in the recovery room.Question 1.What was the last feeling before you fall into sleep? and question 2. Did you feel any pain on your hand during medication injection for anesthesia? Results:There were differences between the groups in terms of total pain score for example in group 1 there were 16 (53%) patients who did not make any movement during rocuronium injection while there were 22 (73%) patients in group 2.There was significant difference in injection rocuronium bromide pain between group 1: dexkethoprofen group, Group 2: control group in terms of the answer to the second question.Patients felt less pain than the control group. Conclusion:The effect of cox inhibitors on rocuronium pain was seen in our study but check is also effective in reducing pain in vascular width.

The Effect of Cognitive Rehabilitation, Physical and Concurrent Training on Sustained, Selective and Shifting Attention in Children with ADHD

Objectives: Attention Deficit/ Hyperactivity Disorder (ADHD) is one of the most common nervous disorders in childhood. The purpose of this study was to investigate effect of cognitive rehabilitation, physical and concurrent training on sustained, selective and shifting attention in ADHD children. Materials and Methods: The study participants included 40 children aged 9-12 years old who were randomly divided into four groups of cognitive rehabilitation training, physical training, combined (physical-cognitive) training and control group. The attendees trained for 16 minutes and each session for 60 minutes. Posttest was performed 24 and 72 hours later. Results: The results of Covariance analysis showed that, the sustained, selective and transitional attention of the combined practice group (physical rehabilitation) have significantly lower error than another group. In the deletion response variable, the mean score of the withdrawal response in the children of the combined exercise group was significantly lower than that of the control group (p <0.05). Conclusion: Overall, the results of this study showed that cognitive rehabilitation and physical trainings can improve attention in children with overactive disorders. But the combination of physical trainings with rehabilitation trainings can improve the types of attention in children with ADHD.

Role of Muscarinic Receptors in Hypoalgesia Induced by Crocin in Neuropathic Pain Rats

Objective. Crocin as an important constituent of saffron has antineuropathic pain properties; however, the exact mechanism of this effect is not known. The aim of this study was whether the hypoalgesic effect of crocin can be exerted through muscarinic receptors. Materials and Methods. In the present project, 36 male Wistar rats (200 ± 20 g) were used. Animals randomly divided into six groups (sham, neuropathy, neuropathy + crocin, neuropathy + atropine 0.5 mg/kg, neuropathy + atropine 1 mg/kg, and neuropathy + atropine 1 mg/kg + crocin). Neuropathy was induced by the chronic constriction injury (CCI) method on the sciatic nerve. Crocin and atropine was administered intraperitoneally during 14 days following the 14th day after surgery. Pain response was detected every three days, two hours after each injection and 3 days following last injection. Mechanical allodynia and thermal hyperalgesia were detected using the Von Frey filaments and plantar test device, respectively. Results. CCI significantly reduced the paw withdrawal response to mechanical and thermal stimulus ( P < 0.01 and P < 0.05 , respectively). Crocin therapy significantly reduced mechanical allodynia and thermal hyperalgesia induced by CCI ( P < 0.05 ). Atropine pretreatment significantly blocked the hypoalgesic effect of crocin ( P < 0.05 in mechanical allodynia and P < 0.01 in thermal hyperalgesia). Fourteen days administration of atropine alone at a dose of 0.5 mg/kg but not 1 mg/kg significantly reduced CCI-induced mechanical allodynia at day 30 after surgery. Conclusion. Crocin significantly decreased CCI-induced neuropathic pain. The hypoalgesic effect of crocin was blocked by atropine pretreatment, which indicates an important role for muscarinic receptors in the effect of crocin.

Stimulus predictability moderates the withdrawal strategy in response to repetitive noxious stimulation in humans

Innate defensive behaviors such as reflexes are found across all species, constituting preprogrammed responses to external threats that are not anticipated. Previous studies indicated that the excitability of the reflex arcs like spinal nociceptive withdrawal reflex (NWR) pathways in humans are modulated by several cognitive factors. This study assesses how the predictability of a threat affects the biomechanical pattern of the withdrawal response, showing that distal and proximal muscles are differentially modulated by descending control.

The Efficacy of Antipyretic Analgesics Administration Intravenously for Preventing Rocuronium-Associated Pain/Withdrawal Response: A Systematic Review and Meta-Analysis

Background: Rocuronium-associated injection pain/withdrawal response (RAIPWR) was non-ideal but occurred frequently when injection intravenously during anesthesia induction. Many studies had reported that pretreating with antipyretic analgesics (AAs) could reduce the occurrence of RAIPWR, but there was no consensus yet. Therefore, this meta-analysis was designed to systematically evaluate the benefits of AAs on RAIPWR in patients. Methods: PubMed, Cochrane Library, Ovid, EMbase, Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data were searched by January 1 st 2019 for randomized controlled trials (RCTs) applying AAs to alleviate RAIPWR in patients underwent elective surgery under general anesthesia. Two investigators assessed quality of RCTs and extracted data respectively and the meta-analysis was carried on Revman 5.3 software. Moreover, we compared AAs in pros and cons directly with lidocaine, the most reported medicine to prevent RAIPWR. Results: Data were analyzed from 9 RCTs totaling 819 patients. The results of Meta-analysis showed that compared to the control group, pretreating with AAs could prevent the total occurrence of RAIPWR [Risk ratio (RR), 0.52; 95% confidence interval (CI), 0.42 to 0.66; P < 0.0001], and took effect on moderate (RR, 0.56; 95%CI, 0.43 to 0.73; P<0.0001) and severe RAIPWR (RR=0.14; 95%CI, 0.08 to 0.24; P<0.00001). When compared to lidocaine, the preventive effect was not so excellent as the latter but injection pain induced by prophylactic occurred less. Conclusion: The currently available evidence suggested that pretreating with AAs intravenously could alleviate RAIPWR.

Interneuronal mechanisms underlying a learning-induced switch in a sensory response that anticipates changes in behavioural outcomes

ABSTRACTHow an animal responds to a particular sensory stimulus will to a great extent depend on prior experience associated with that stimulus. For instance, aversive associative learning may lead to a change in the predicted outcomes, which suppresses the behavioural response to an otherwise rewarding stimulus. However, the neuronal mechanisms of how aversive learning can result in the suppression of even a vitally important innate behaviour is not well understood. Here we used the model system of Lymnaea stagnalis to address the question of how an anticipated aversive outcome can alter the behavioural response to a previously effective feeding stimulus. We found that aversive classical conditioning with sucrose as the CS (conditioned stimulus) and strong touch as the aversive US (unconditioned stimulus) reverses the decision so that the same salient feeding stimulus inhibits feeding, rather than activating it. Key to the understanding of the neural mechanism underlying this switch in the behavioural response is the PlB (pleural buccal) extrinsic interneuron of the feeding network whose modulatory effects on the feeding circuit inhibit feeding. After associative aversive training, PlB is excited by sucrose to reverse its effects on the feeding response. Aversive associative learning induces a persistent change in the electrical properties of PlB that is both sufficient and necessary for the switch in the behavioural output. In addition, the strong touch used as the US during the associative training protocol can also serve as a sensitizing stimulus to lead to an enhanced defensive withdrawal response to a mild touch stimulus. This non-associative effect of the strong touch is probably based on the facilitated excitatory output of a key identified interneuron of the defensive withdrawal network, PeD12.

The Efficacy of Antipyretic Analgesics Administration Intravenously for Preventing Rocuronium-Associated Pain/Withdrawal Response: A Systematic Review and Meta-Analysis

Background: Rocuronium-associated injection pain/withdrawal response (RAIPWR) was non-ideal but occurred frequently when injection intravenously during anesthesia induction. Many studies had reported that pretreating with antipyretic analgesics (AAs) could reduce the occurrence of RAIPWR, but there was no consensus yet. Therefore, this meta-analysis was designed to systematically evaluate the benefits of AAs on RAIPWR in patients. Methods: PubMed, Cochrane Library, Ovid, EMbase, Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data were searched by January 1st 2019 for randomized controlled trials (RCTs) applying AAs to alleviate RAIPWR in patients underwent elective surgery under general anesthesia. Two investigators assessed quality of RCTs and extracted data respectively and the meta-analysis was carried on Revman 5.3 software. Moreover, we compared AAs in pros and cons directly with lidocaine, the most reported medicine to prevent RAIPWR. Results: Data were analyzed from 9 RCTs totaling 819 patients. The results of Meta-analysis showed that compared to the control group, pretreating with AAs could prevent the total occurrence of RAIPWR [Risk ratio (RR), 0.52; 95% confidence interval (CI), 0.42 to 0.66; P < 0.0001], and took effect on moderate (RR, 0.56; 95%CI, 0.43 to 0.73; P<0.0001) and severe RAIPWR (RR=0.14; 95%CI, 0.08 to 0.24; P<0.00001). When compared to lidocaine, the preventive effect was not so excellent as the latter but injection pain induced by prophylactic occurred less. Conclusion: The currently available evidence suggested that pretreating with AAs intravenously could alleviate RAIPWR.