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Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.
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OBJECTIVE: This analysis reports the healthcare professional global assessment (HPGA) and patient global assessment (PGA) scores and the adverse event (AE) profile by age, body mass index (BMI), sex, and race from the three Phase III registration studies for sufentanil sublingual tablet (SST) 30 mcg. METHODS: Global assessments and treatment-related AEs were analyzed from patients treated with SST 30 mcg for moderate-to-severe acute pain following surgery or in the emergency department (ED). Pooled data were analyzed across patient demographic subgroups. RESULTS: A total of 283 patients were included in the HPGA/PGA analyses. The majority underwent abdominal surgery, with the remaining patients undergoing orthopedic or "other" types of surgery. Overall, SST 30 mcg was highly rated by both healthcare professionals and patients across the demographic subgroups. A total of 323 patients were included in the safety evaluation. The majority of patients did not experience any SST-related AEs; however, those that did experienced common opioid-related side effects such as nausea, headache, dizziness, and vomiting. No patients experienced unexpected AEs or required the use of naloxone. CONCLUSION: SST 30 mcg was highly rated and well tolerated across demographic subgroups with the majority of patients not experiencing any adverse event related to SST 30 mcg. These findings support the use of sublingual sufentanil in all adult patients, regardless of age, BMI, sex, or race for the treatment of moderate-to-severe acute pain.
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Objective: To evaluate sufentanil sublingual tablet 30 mcg (SST 30 mcg) for postoperative pain in an older patient population with comorbidities. Design: Multicenter, open-label, single-arm study. Setting: Nine hospitals across the United States. Subjects: Adults aged ≥40 years who had undergone a surgical procedure. Methods: Patients with a postoperative pain intensity score ≥4 on an 11-point numeric rating scale (NRS) were allowed to enter the study and receive SST 30 mcg as requested for pain (minimum 60-minute redosing interval) over the 12-hour study period. Efficacy was assessed by patient reports of pain intensity on the NRS and a five-point pain relief scale. Safety was monitored throughout the study; plasma sufentanil concentrations were also measured. The primary efficacy endpoint was the time-weighted summed pain intensity difference (SPID) to baseline over 12 hours (SPID12). Results: Of the 140 patients enrolled, 69% were American Society of Anesthesiologists Physical Class II or III, 44% had a body mass index (BMI) ≥30 mg/kg2, and 29% had hepatic and/or renal impairment. Average age was 54.7 years (SD = 9.9 years), and average baseline pain intensity was 6.2 (SD = 1.9). The most common surgeries were abdominal (59%) and orthopedic (20%). The mean SPID12 was 36.0 (standard error of the mean = 2.2); mean scores were similar, regardless of age, sex, race, and BMI. From baseline, mean pain intensity decreased significantly starting 30 minutes postdose, and mean pain relief increased significantly starting 15 minutes postdose, remaining relatively stable through 12 hours (P < 0.001 at each time point). Four (3%) patients discontinued due to inadequate analgesia, and 45 (32%) patients had one or more adverse events that were considered possibly or probably related to the study drug. Mean plasma sufentanil concentrations were generally similar regardless of age, sex, BMI, or organ impairment status. Conclusions: SST 30 mcg was effective and well tolerated for the management of moderate-to-severe acute postoperative pain.
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Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Sufentanil/uso terapêutico , Administração Sublingual , Idoso , Artroplastia de Quadril , Artroplastia do Joelho , Feminino , Humanos , Laparoscopia , Laparotomia , Hepatopatias , Masculino , Mamoplastia , Pessoa de Meia-Idade , Medição da Dor , Insuficiência RenalRESUMO
OBJECTIVE: To conduct a systematic literature review (SLR) and quantitative analysis to assess the comparative efficacy and safety of the sufentanil sublingual tablet system (SSTS) against other available patient controlled analgesia (PCA) options for post-operative analgesia. METHODS: An SLR was conducted for studies published between 2004 and 2016. Due to study heterogeneity, subgroup analyses were conducted controlling for differences in imputation methods for missing values, baseline pain severity, and type of surgery. Where sufficient data was available, a mixed treatment comparison (MTC) was performed. RESULTS: The MTC and subgroup analyses used 13 studies. In direct meta-analysis, there was a statistically significant difference in favor of SSTS compared with intravenous (IV) PCA (morphine) at 24 hours for the patient global assessment (PGA) scores of "good" or "excellent". For the Pain Intensity Score, there were numerical but not statistically significant differences in favor of the SSTS versus IV PCA (morphine) and the patient controlled transdermal system (PCTS) (fentanyl) in the MTC at 6 hours (standardized mean difference -0.27 [credible interval -2.78, 2.09] and -0.36 [-3.89, 3.03], respectively). The onset of pain relief was earlier with the SSTS versus IV PCA (morphine) as shown by the Pain Intensity Difference. Likewise, the onset was earlier compared with PCTS (fentanyl) where data was available. There was a significant difference in favor of SSTS compared with IV PCA (morphine) and with PCTS (fentanyl) for any adverse event, and numerical improvements for withdrawals due to adverse events. CONCLUSIONS: This meta-analysis shows that SSTS is an option for non-invasive management of moderate-to-severe post-operative pain which can be more effective, faster in onset and better tolerated than IV PCA (morphine) and PCTS (fentanyl).
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Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Sufentanil/administração & dosagem , Dor Aguda/tratamento farmacológico , Administração Cutânea , Administração Sublingual , Fentanila/administração & dosagem , Humanos , Morfina/administração & dosagem , Medição da Dor , Comprimidos/uso terapêutico , Adesivo TransdérmicoRESUMO
BACKGROUND: Results from a phase-3, prospective, randomized, double-blind, placebo-controlled trial evaluating sufentanil sublingual tablet 30 mcg (SST) for the management of pain after ambulatory abdominal surgery are presented. METHODS: Adults with American Society of Anesthesiologists status 1 to 3 scheduled to undergo abdominoplasty, open tension-free inguinal hernioplasty, or laparoscopic abdominal surgery under general or spinal anesthesia that did not include intrathecal opioids during the operation were eligible. Opioid-tolerant patients were excluded. The primary endpoint was the time-weighted summed pain intensity difference to baseline (SPID) over 12 hours. Secondary endpoints included SPID over 24 and 48 hours, total pain relief, and patient and healthcare professional (HCP) global assessments. RESULTS: Overall, 161 patients were randomized to SST (N = 107) or placebo (N = 54); pain scores were recorded for up to 48 hours. SPID 12 was higher (greater pain intensity reduction from baseline) in the SST group compared with placebo (25.8 vs. 13.1; P < 0.001, with a difference of 12.7 [95% confidence interval 7.16, 18.23]). In the SST group, a greater proportion of patients and HCPs responded "good" or "excellent" on the global assessments compared with placebo (P < 0.001 for both). There was a numerically, but not statistically, higher incidence of nausea and headache in the SST group. CONCLUSIONS: In patients following abdominal surgery in an ambulatory care setting, SST was an effective opioid analgesic in postoperative pain management. In addition, SST was well tolerated with mild-to-moderate side effects, similar to those found in placebo-treated patients.
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Abdome/cirurgia , Analgésicos Opioides/administração & dosagem , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Sufentanil/administração & dosagem , Administração Sublingual , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/tendências , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Estudos Prospectivos , Comprimidos/uso terapêuticoRESUMO
Opioid administration delivered intravenously (IV) by patient-controlled analgesia (PCA) devices has been an important development in addressing insufficient management of acute pain in the postsurgical setting. However, IV PCA has several disadvantages, including operator error, risk of patient exposure to analgesic gaps, IV line patency issues, and risk of catheter-related infection, all of which contribute to the total cost of care. Morphine, the most commonly used opioid in IV PCA, has a relatively slow onset of analgesia, which may leave patients with inadequate initial pain control and at risk of opioid dose-stacking. Sufentanil is an opioid with no major active metabolites and a rapid onset of analgesia. The sufentanil sublingual tablet system (SSTS) with a 20-minute lockout and other safety features is a novel noninvasive PCA system in development for on-demand relief of moderate to severe acute pain in the hospital setting. Data from phase 3 trials of the use of SSTS after elective major open abdominal and orthopedic surgery show that analgesia is rapidly achieved, with a longer mean interdosing interval compared with IV PCA morphine (81 vs 47 minutes) and a high level of patient and nurse satisfaction. These data suggest that SSTS may also aid in the avoidance of some of the pitfalls inherent with IV PCA, which may help reduce hospital costs associated with IV PCA-related issues. This article describes the evolution, benefits, issues, and costs associated with IV PCA and reviews data from preclinical studies of sufentanil through SSTS phase 3 trials.
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BACKGROUND: Complications with IV patient-controlled analgesia include programming errors, invasive access, and impairment of mobility. This study evaluated an investigational sufentanil sublingual tablet system (SSTS) for the management of pain after knee or hip arthroplasty. METHODS: This prospective, randomized, parallel-arm, double-blind study randomized postoperative patients at 34 U.S. sites to receive SSTS 15 µg (n = 315) or an identical placebo system (n = 104) and pain scores were recorded for up to 72 h. Adult patients with American Society of Anesthesiologists status 1 to 3 after primary total unilateral knee or hip replacement under general anesthesia or with spinal anesthesia that did not include intrathecal opioids were eligible. Patients were excluded if they were opioid tolerant. The primary endpoint was the time-weighted summed pain intensity difference to baseline over 48 h. Secondary endpoints included total pain relief, patient and healthcare professional global assessments, and patient and nurse ease-of-care questionnaires. RESULTS: Summed pain intensity difference (standard error) was higher (better) in the SSTS group compared with placebo (76 [7] vs. -11 [11], difference 88 [95% CI, 66 to 109]; P < 0.001). In the SSTS group, more patients and nurses responded "good" or "excellent" on the global assessments compared with placebo (P < 0.001). Patient and nurse ease-of-care ratings for the system were high in both groups. There was a higher incidence of nausea and pruritus in the SSTS group. CONCLUSION: SSTS could be an effective patient-controlled pain management modality in patients after major orthopedic surgery and is easy to use by both patients and healthcare professionals.
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Analgésicos Opioides/administração & dosagem , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Manejo da Dor/métodos , Dor Pós-Operatória/prevenção & controle , Sufentanil/administração & dosagem , Administração Sublingual , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Estudos ProspectivosRESUMO
Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.
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Dor Crônica/terapia , Ensaios Clínicos como Assunto/normas , Manejo da Dor/normas , Guias de Prática Clínica como Assunto/normas , Projetos de Pesquisa/normas , Pesquisa Biomédica/métodos , Pesquisa Biomédica/normas , Dor Crônica/diagnóstico , Ensaios Clínicos como Assunto/métodos , Congressos como Assunto/normas , Humanos , Manejo da Dor/métodos , Fatores de TempoRESUMO
BACKGROUND AND OBJECTIVES: This study evaluates the efficacy and safety of a sufentanil sublingual tablet system (SSTS) for the management of postoperative pain following open abdominal surgery. METHODS: At 13 hospital sites in the United States, patients following surgery with pain intensity of greater than 4 on an 11-point numerical rating scale were randomized to receive SSTS dispensing a 15-µg sufentanil tablet sublingually with a 20-minute lockout or an identical system dispensing a placebo tablet sublingually. Pain intensity scores were recorded at baseline and for up to 72 hours after starting study drug. The primary end point was time-weighted summed pain intensity difference (SPID) over 48 hours. Secondary end points included SPID and total pain relief (TOTPAR) for up to 72 hours and patient and health care provider global assessments of the method of pain control. RESULTS: Summed pain intensity difference over 48 hours was significantly higher in the SSTS group than in the placebo group (least squares mean [SEM], 105.60 [10.14] vs 55.58 [13.11]; P = 0.001). Mean SPID and TOTPAR scores were significantly higher in the SSTS group at all time points from 1 hour (SPID) or 2 hours (TOTPAR) until 72 hours (P < 0.05). In the SSTS group, patient global assessment and health care provider global assessment ratings of good or excellent were greater than placebo at all time points (P < 0.01). Safety parameters, including adverse events and vital signs, were similar for SSTS and placebo. CONCLUSIONS: These results suggest that SSTS is effective and safe for the management of postoperative pain in patients following open abdominal surgery.
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Abdome/cirurgia , Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/administração & dosagem , Manejo da Dor/métodos , Dor Pós-Operatória/prevenção & controle , Sufentanil/administração & dosagem , Administração Sublingual , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/diagnóstico , Comprimidos , Adulto JovemRESUMO
BACKGROUND: Sufentanil sublingual microtablets (SSMs) at a dose of 15 µg per tablet have been studied for postoperative patient-controlled analgesia with a 20-minute lockout via a bedside handheld system over 2 days to 3 days of use. For more short-term (<24 hours) management of acute moderate-to-severe pain, such as in the ambulatory surgical setting, a single, higher-strength SSM dose administered via a health care provider would be of benefit as it would require less frequent administration and avoid the setup of a drug delivery system. METHODS: This study was a two-center, randomized, double-blind, placebo-controlled trial for 12 hours in patients 18 years to 80 years of age who were undergoing bunionectomy alone or with hammertoe repair. Patients were randomly assigned at a 2:2:1 ratio to treatment with SSM 20 µg, SSM 30 µg, or placebo. The primary endpoint was time-weighted summed pain intensity difference to baseline over 12 hours (SPID12). Patients had to have a pain intensity score of 4 or higher just before initial microtablet dosing. Additional doses were administered when requested by the patient, with a minimum redosing interval of 1 hour. RESULTS: One hundred patients were randomized and received study drug. The SSM 30 µg was superior in the treatment of postbunionectomy surgical pain compared with placebo as demonstrated by the SPID12 score (6.53 vs. -7.12, respectively; p = 0.003) as well as all other secondary efficacy end points. The SSM 20-µg dosage strength was not superior to placebo for primary or secondary efficacy measures. Adverse events were similar among the three groups with the exception of nausea, vomiting, and somnolence, which demonstrated a dose-dependent increase in occurrence. CONCLUSION: The SSM 30 µg may be an effective, noninvasive alternative to health care provider-administered intravenous, intramuscular, or oral opioids for the management of moderate-to-severe acute pain. LEVEL OF EVIDENCE: Therapeutic study, level I.
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Analgésicos Opioides/administração & dosagem , Hallux Valgus/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Sufentanil/administração & dosagem , Administração Sublingual , Idoso , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sufentanil/uso terapêutico , ComprimidosRESUMO
BACKGROUND: Problems with intravenous patient-controlled analgesia (IV PCA) are well known, including invasive route of delivery and pump programming errors. The primary objective of this study was to evaluate patient satisfaction with a novel sublingual sufentanil PCA system (sufentanil sublingual tablet system 15 mcg with a 20-minute lockout interval; SSTS) to IV PCA morphine sulfate 1 mg with a 6-minute lockout interval (IV PCA MS) for the management of acute postoperative pain. METHODS: This was a randomized, open-label, 48-hour non-inferiority study with optional extension to 72 hours at 26 U.S. sites enrolling patients scheduled for elective major open abdominal or orthopedic (hip or knee replacement) surgery. The primary outcome measure was the proportion of patients who responded "good" or "excellent" (collectively "success") at the 48-hour timepoint on the Patient Global Assessment of method of pain control (PGA48). RESULTS: A total of 357 patients received study drug and 78.5% vs. 65.6% of patients achieved PGA48 "success" for SSTS vs. IV PCA MS, respectively, demonstrating non-inferiority (P < 0.001 using the one-side Z-test against the non-inferiority margin) as well as statistical superiority for treatment effect (P = 0.007). Patients using SSTS reported more rapid onset of analgesia and patient and nurse ease of care and satisfaction scores were higher than IV PCA MS. Adverse events were similar between the 2 groups; however, SSTS had fewer patients experiencing oxygen desaturations below 95% compared to IV PCA MS (P = 0.028). CONCLUSIONS: Sufentanil sublingual tablet system is a promising new analgesic technology that may address some of the concerns with IV PCA.
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Analgésicos Opioides/uso terapêutico , Morfina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Sufentanil/uso terapêutico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Morfina/efeitos adversos , Medição da Dor , Sufentanil/administração & dosagem , Sufentanil/efeitos adversos , Comprimidos/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Intravenous patient-controlled analgesia (PCA) equipment and opioid cost analyses on specific procedures are lacking. This study estimates the intravenous PCA hospital cost for the first 48 postoperative hours for three inpatient surgeries. METHODS: Descriptive analyses using the Premier database (2010-2012) of more than 500 US hospitals were conducted on cost (direct acquisition and indirect cost for the hospital, such as overhead, labor, pharmacy services) of intravenous PCA after total knee/hip arthroplasty (TKA/THA) or open abdominal surgery. Weighted average cost of equipment and opioid drug and the literature-based cost of adverse events and complications were aggregated for total costs. RESULTS: Of 11,805,513 patients, 272,443 (2.3%), 139,275 (1.2%), and 195,062 (1.7%) had TKA, THA, and abdominal surgery, respectively, with approximately 20% of orthopedic and 29% of abdominal patients having specific intravenous PCA database cost entries. Morphine (57%) and hydromorphone (44%) were the most frequently used PCA drugs, with a mean cost per 30 cc syringe of $16 (30 mg) and $21 (6 mg), respectively. The mean number of syringes used for morphine and hydromorphone in the first 48 hours were 1.9 and 3.2 (TKA), 2.0 and 4.2 (THA), and 2.5 and 3.9 (abdominal surgery), respectively. Average costs of PCA pump, intravenous tubing set, and drug ranged from $46 to $48, from $20 to $22, and from $33 to $46, respectively. Pump, tubing, and saline required to maintain patency of the intravenous PCA catheter over 48 hours ranged from $9 to $13, from $8 to $9, and from $20 to $22, respectively. Supplemental non-PCA opioid use ranged from $56 for THA to $87 for abdominal surgery. Aggregated mean intravenous PCA equipment and opioid cost per patient were $196 (THA), $204 (TKA), and $243 (abdominal surgery). Total costs, including for adverse events, complications, and intravenous PCA errors, ranged from $647 to $694. CONCLUSION: Although there is variation between different types of surgery, the hospital cost of intravenous PCA after major surgery is substantial. Novel technology should demonstrate cost-effectiveness in addition to clinical superiority.
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BACKGROUND AND OBJECTIVES: A sublingual sufentanil tablet is being developed as a potential alternative to intravenous (IV) opioids for the management of postoperative pain. The objective of these studies was to evaluate the pharmacokinetics, efficacy, and safety of sublingual sufentanil tablets for postoperative pain management. METHODS: The pharmacokinetics of sublingual sufentanil 10 and 80 µg were compared with IV sufentanil in 12 subjects in a phase 1 study. The safety and efficacy of sublingual sufentanil (5-15 µg) were evaluated in double-blind, randomized, placebo-controlled phase 2 studies in patients undergoing knee replacement surgery (n = 101) or open abdominal (ABD) surgery (n = 94). The primary efficacy measurement was the summed pain intensity difference compared with baseline over 12 hours (SPID-12). RESULTS: Sublingual sufentanil pharmacokinetics were dose proportional following single doses of 10 and 80 µg. Plasma half-time (time from peak plasma concentration to 50% of peak concentration) was 80 to 90 minutes for sublingual sufentanil compared with 15 minutes or less for IV sufentanil. In the phase 2 studies, greater SPID-12 scores (ie, lower pain intensity) compared with placebo were observed for sublingual sufentanil 15 µg in the knee replacement study (P < 0.05) and for 10 and 15 µg in the ABD study (P < 0.01). All doses of sublingual sufentanil were well tolerated, and the incidence of adverse events was similar between the sublingual sufentanil and placebo groups. CONCLUSIONS: Sufentanil formulated as a sublingual solid dosage form provides a duration of action that allows effective analgesia for postoperative patients in a medically supervised setting.
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Abdome/cirurgia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacocinética , Artroplastia do Joelho/efeitos adversos , Dor Pós-Operatória/prevenção & controle , Sufentanil/administração & dosagem , Sufentanil/farmacocinética , Administração Sublingual , Adulto , Idoso , Analgésicos Opioides/efeitos adversos , Análise de Variância , Área Sob a Curva , Disponibilidade Biológica , Feminino , Meia-Vida , Humanos , Infusões Intravenosas , Análise dos Mínimos Quadrados , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/diagnóstico , Sufentanil/efeitos adversos , Comprimidos , Resultado do Tratamento , Adulto JovemRESUMO
Patients undergoing thyroidectomy with neck fully extended usually experience occipital headache and posterior neck pain. We have attempted to evaluate the effect of preoperative greater occipital nerve (GON) block on occipital headache and posterior neck pain after thyroidectomy. Eighty-two patients undergoing elective total thyroidectomy were randomly allocated to two groups. In block group, bilateral GON blocks with 0.25% bupivacaine were performed. The control group did not have any prior block. Occipital headache and posterior neck stiffness were assessed using the visual analogue scale (VAS) and verbal rating scale. VAS of occipital headache and posterior neck pain in block group was significantly lower compared to that in the control group at postoperative 12 and 24 hours (p < 0.05). In addition, the proportion of patients reporting moderate or severe occipital headache and posterior neck pain at postoperative 12 and 24 hours in block group was significantly lower than that in control group (p < 0.001). No side effects were observed during and after GON block. We conclude that preoperative GON block with 0.25% bupivacaine is an effective technique to reduce occipital headache and posterior neck pain after thyroid surgery.
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Cefaleia/etiologia , Cervicalgia/terapia , Bloqueio Nervoso , Tireoidectomia/métodos , Adolescente , Adulto , Anestésicos Locais/farmacologia , Bupivacaína/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Dor , Medição da Dor , Complicações Pós-Operatórias , Resultado do TratamentoRESUMO
The regulators of G protein signaling (RGS) are a family of proteins with conserved RGS domains and play essential roles in regulating G protein-mediated signal transduction and physiological events. GAIP/RGS19 (G alpha interacting protein, also classified as RGS19), a member of the RGS family, has been shown to negatively regulate the signaling of many G protein-coupled receptors, including the opioid receptors. Two GAIP/RGS19 mRNA variants, resulted from an alternative splicing of exon 2 of the GAIP/RGS19 gene, were identified in multiple mouse tissues. One of the transcripts consists of a complete set of exons and encodes a full-length GAIP/RGS19 protein, and the other does not have exon 2 and therefore encodes an N-terminal 22 residue truncated short GAIP/RGS19 protein. When co-expressed with either the opioid-receptor-like (ORL1) receptor or one of the mu, delta, and kappa opioid receptors, by transfecting dual-expression plasmids into COS-7 cells, the full-length GAIP/RGS19 was more effective than the N-terminally truncated variant and was more selective in regulating the ORL1 receptor signaling than in regulating the mu, delta, and kappa opioid receptors, as measured by the effectiveness to increase the agonist-stimulated GTPase activity and to reverse the agonist-induced inhibition of cyclic AMP accumulation. In the same assays, the N-terminally truncated GAIP/RGS19 did not distinguish ORL1 from the mu, delta, and kappa opioid receptors. In contrast, co-expression of RGS4 with either ORL1 or opioid receptors showed the selectivity of RGS4 for regulating opioid receptors was mu > kappa > delta > ORL1, an order completely different from that of GAIP/RGS19. The results suggest that GAIP/RGS19 prefers regulating ORL1 receptor signaling over other opioid receptors, and that the N-terminal domain of GAIP/RGS19 plays a crucial role in its receptor preference.
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Processamento Alternativo , Proteínas RGS/fisiologia , Receptores Opioides/metabolismo , Transdução de Sinais , Animais , Células COS , Chlorocebus aethiops , AMP Cíclico/metabolismo , Guanosina Trifosfato/metabolismo , Camundongos , Estrutura Terciária de Proteína , Proteínas RGS/genética , RNA Mensageiro/análise , Receptores Opioides/genética , Transfecção , Receptor de NociceptinaRESUMO
The purpose of this study was to determine whether the 5-hydroxytryptamine7 (5-HT7) receptor is expressed by nociceptor-like neurons in the rat PNS and whether 5-HT activates these nociceptors via the 5-HT7 receptor subtype. Using a polyclonal antibody and the method of immunofluorescence staining, we demonstrated that the 5-HT7 receptor appears predominately on "nociceptor-like" neurons of the rat lumbar dorsal root ganglia. Using immunocytochemical methods, we showed that the immunoreactivity of the 5-HT7 receptor antibody complex is localized in the superficial layers of the spinal cord dorsal horn, which corresponds with laminae I, IIouter and IIinner. Furthermore, we demonstrated that noxious stimulation produced by knee injection of 5-HT or a 5-HT7 agonist dose-dependently increases c-Fos production of the rat spinal cord dorsal horn. This effect was significantly inhibited by the preinjection of a 5-HT7 antagonist. We conclude that the 5-HT7 receptor is expressed by rat primary afferent nociceptors which terminate in the superficial layers of the spinal cord dorsal horn and that the 5-HT7 receptor subtype is involved in nociceptor activation by 5-HT.