Pathological pain or clinical pain is caused by tissue and nerve injuries, and is usually chronic and mainly divided into inflammatory pain and neuropathic pain. Pathological pain is typically characterized by hyperalgesia (increased responsiveness to noxious stimuli) and allodynia (painful responses to normally innocuous stimuli). The mitogen-activated proteins kinases (MAPKs) are a family of evolutionally conserved molecules that play a critical role in cell signaling, consisting of extracellular signal regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), which play an important role in neural plasticity of pathological pain. Inhibition of MAPKs alleviates inflammatory pain and neuropathic pain in different animal models. It is very important to study the inhibition of MAPKs as a therapeutic approach to treat pathological pain. 相似文献
Leucettamols, bifunctionalized sphingoid-like compounds obtained from a marine sponge Leucetta sp., act as non-electrophilic activators of the TRPA1 channel and potent inhibitors of the icilin-mediated activation of the TRPM8 channel, while they are inactive on CB1, CB2 and TRPV1 receptors. Leucettamols represent the first compounds of marine origin to target TRPA1 and the first class of natural products to inhibit TRPM8 channels. The preparation of a small series of semi-synthetic derivatives revealed interesting details on the structure-activity relationships within this new chemotype of simple acyclic TRP modulators. 相似文献
Objective To study the analgesic potency of the α2‐agonist romifidine in the horse using both an electrical current and a mechanical pressure model for nociceptive threshold testing. In addition, a comparison was made with doses of detomidine and xylazine that produce equivalent degrees of sedation. Study design Randomized, placebo‐controlled, blinded cross‐over study. Animals Six adult Swiss warmblood horses, one mare and five geldings, weighing from 530 to 650 kg and aged 6–15 years. Methods Nociceptive thresholds were measured using an electrical stimulus applied to the coronary band and using a pneumatically operated pin pressing on the cannon bone. Measurements were made immediately before and every 15 minutes for 2 hours after IV injection of the test substances. Lifting of the foot indicated the test end point. Results The three α2‐agonists caused a temporary increase in nociceptive thresholds with a maximal effect within 15 minutes and a return to baseline levels within 1 hour. Using electrical current testing nociceptive thresholds were significantly different from placebo (mean ± SD) for detomidine at 15 minutes (from control 5.8 ± 0.9 to 23.3 ± 3.9 mA, p = 0.0066) and 30 minutes (from control 6.6 ± 1.1 to 18.8 ± 3.3 mA, p = 0.0091). The difference was significant for romifidine at 15 minutes only (from control 5.8 ± 0.9 to 18.7 ± 3.8 mA, p = 0.0066). With mechanical pressure testing nociceptive thresholds were significantly different from control for detomidine at 15 minutes (from 3.2 ± 0.2 to 6.2 ± 0.5 N, p = 0.00076) and 30 minutes (from 3.2 ± 0.7 to 5.7 ± 0.8 N, p = 0.0167). The difference was significant for xylazine at 15 minutes (from control 3.2 ± 0.2 to 5.6 ± 0.7 N, p = 0.0079). At 15 minutes the order of magnitude of the measured antinociceptive effect was significantly different between the two pain tests for both romifidine and detomidine, but not for xylazine. For romifidine, the increase of mean thresholds compared to placebo was 4.0 ± 1.3 times placebo levels with the electrical current test compared to 1.3 ± 0.3 times for the mechanical pressure test (p = 0.037). For detomidine, the increase of mean thresholds compared to placebo was 5.4 ± 1.7 times control levels with the electrical current test compared to 2.0 ± 0.2 times for the mechanical pressure test (p = 0.040). This represents a 2.7 (romifidine) and 3.4 times (detomidine) greater increase in thresholds using electrical current testing compared to the use of mechanical pressure testing. Conclusion and clinical relevance This study demonstrates the analgesic potential of α2‐agonists in the horse for somatic pain and that they can have quantitatively different antinociceptive effects according to the antinociceptive test used. 相似文献
ObjectiveTo compare the quality of postoperative analgesia and sedation after preoperative saphenous and sciatic nerve blockade, preoperative lumbosacral epidural injection and perioperative intravenous (IV) morphine, lidocaine and ketamine infusions in dogs undergoing stifle arthroscopy and tibial plateau leveling osteotomy (TPLO) under general anesthesia.Study designProspective, blinded, randomized, clinical comparison study.AnimalsA total of 45 dogs weighing 33.9 (15.9–56.7) kg and aged 5.2 (1.0–12.0) years, mean (range), undergoing elective unilateral TPLO for spontaneous cranial cruciate ligament rupture.MethodsClient-owned dogs were enrolled. Dogs were randomly assigned to one of three groups: group MLK, perioperative IV morphine, lidocaine and ketamine infusion; group EPID, lumbosacral epidural with ropivacaine and morphine; or group SSNB, saphenous and sciatic nerve blockade with ropivacaine. Routine stifle arthroscopy followed by TPLO surgery was performed. Sedation and pain scores were assessed at 0, 2, 4, 8 and 24 hours following extubation. Rescue analgesia was administered as prescribed by Glasgow composite pain score–short form score >5.ResultsSedation scores for MLK were higher than EPID and SSNB. Pain scores for SSNB were lower than those for EPID and MLK. No significant differences were found in anesthesia duration or surgery duration among groups. No dogs required rescue analgesia.Conclusions and clinical relevanceAlthough analgesia was adequate in all groups, the best combination of analgesia without increased sedation was recorded for SSNB. 相似文献
ObjectiveTo determine whether L-carvone increases the voltage threshold response to a noxious electrical stimulus in sheep.Study designProspective, blinded, randomized, crossover experimental study.AnimalsA group of six healthy adult sheep.MethodsSheep were instrumented with cranial dorsothoracic subcutaneous copper electrodes. A stimulator delivered a 10 ms square-wave stimulus at 50 pps starting at 0.1 V with a 0.2 V second–1 ramp. The stimulus stopped once two observers who were blinded to treatment noted a behavioral pain response or when a 15 V cut-off was reached. Next, 0.15 mL kg–1 of either a 50% L-carvone solution or a saline-vehicle control was administered intramuscularly, and electrical threshold responses were measured every 5–15 minutes over a 6 hour period using methods identical to the baseline. One week following the first treatment (L-carvone or control), sheep were studied using identical methods with the second treatment (control or L-carvone). Drug and time effects were evaluated using a two-way repeated measures analysis of variance, and pairwise comparisons were evaluated with Holm-Sidák tests with values of p < 0.05 considered significant.ResultsL-carvone significantly increased voltage threshold responses for most time points up to 75 minutes compared with baseline and with saline control. The last time point with a significantly different response between L-carvone and saline treatments was 5 hours after drug administration. The saline-vehicle control decreased voltage threshold responses at several time points after 3 hours.Conclusions and clinical relevanceIntramuscular L-carvone is analgesic in sheep, although the ethanol-propylene glycol vehicle may cause mild hyperalgesia. This study demonstrates that a food-derived compound can be used to relieve pain in a food-producing animal. 相似文献
Chiari‐like malformation (CM) and syringomyelia (SM) cause a pain syndrome in Cavalier King Charles spaniels (CKCS). Clinical signs are not consistently apparent on neurologic examination, and owner reporting of signs provides vital clinical history. However, owner questionnaires for this disease are not well developed.
Objectives
To develop a tool to capture owner‐reported clinical signs for use in clinical trials and to compare owner‐reported signs with the presence of pain on neurologic examination and SM on magnetic resonance imaging (MRI).
Animals
Fifty client‐owned CKCS.
Methods
Owners completed a questionnaire and pain/scratch map. Each dog underwent a neurologic examination and craniocervical magnetic resonance imaging (MRI). Questionnaire responses were developed into scores, area of shading for pain/scratch maps was measured, and consistency of responses between these tools was assessed. Owner‐reported findings were compared with neurologic examination findings and presence and severity of SM on MRI.
Results
Thirty‐three dogs were symptomatic and 17 asymptomatic; 30 had SM. The most common sign of pain was crying out when lifted (n = 11). Extent of shaded areas on maps positively correlated with questionnaire scores for pain (r2 = 0.213, P =0.006) and scratch (r2 = 0.104, P =0.089). Owner‐reported findings were not significantly associated with presence or severity of SM or neurologic examination findings. Owner‐reported lateralization of signs was significantly associated with SM lateralization (P <0.0001).
Conclusions
The questionnaire and maps may be useful for clinical trials. Lack of association of owner‐reported signs with SM highlights our lack of understanding of the pathophysiology of pain in this disease. 相似文献
AIM: To survey the attitudes and perceptions of veterinary paraprofessionals in New Zealand to postoperative pain in dogs and cats.
METHODS: In December 2011, veterinary paraprofessionals (VP) from throughout New Zealand were invited to participate in an online survey. Eleven questions, which were divided into five sections, were used to determine demographic information, the respondents’ assessment of pain after commonly performed surgeries in dogs and cats, their opinions on provision of analgesia, who had responsibility for pain monitoring and the use of any formal pain scoring system in the practice.
RESULTS: Data from 165 respondents were able to be used, and 162 (98%) respondents to the survey were female. According to the respondents’ estimates, fracture repair in dogs and repair of diaphragmatic hernias in cats had the highest pain score following surgery. Neutering procedures involving dogs were scored higher than for cats (p<0.01). All respondents agreed that animals benefit from perioperative analgesia. The veterinary nurse was reported to be predominantly responsible for monitoring pain in animals postoperatively by 116/165 (70.3%) respondents. Of 165 respondents, 154 (93%) considered that their knowledge of pain and assessment of pain could be enhanced.
CONCLUSIONS: This survey reflects the attitudes and perceptions of a sample of VP in New Zealand to postoperative pain in dogs and cats. The results indicate that all respondents believe that surgery results in sufficient pain to warrant analgesic therapy. Routine neutering surgeries were considered to be more painful in dogs than in cats. The current survey also provides information to educators on potential areas of focus, given that 93% of respondents felt that their knowledge of pain and assessment of pain could be enhanced. 相似文献