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1.
Mol Pain ; 17: 1744806921997206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33829907

RESUMO

Beta 2 adrenergic receptor (ß2 AR) activation in the central and peripheral nervous system has been implicated in nociceptive processing in acute and chronic pain settings with anti-inflammatory and anti-allodynic effects of ß2-AR mimetics reported in several pain states. In the current study, we examined the therapeutic efficacy of the ß2-AR agonist clenbuterol in a rat model of persistent postsurgical hypersensitivity induced by disruption of descending noradrenergic signaling in rats with plantar incision. We used growth curve modeling of ipsilateral mechanical paw withdrawal thresholds following incision to examine effects of treatment on postoperative trajectories. Depletion of spinal noradrenergic neurons delayed recovery of hypersensitivity following incision evident as a flattened slope compared to non-depleted rats (-1.8 g/day with 95% CI -2.4 to -1.085, p < 0.0001). Chronic administration of clenbuterol reduced mechanical hypersensitivity evident as a greater initial intercept in noradrenergic depleted (6.2 g with 95% CI 1.6 to 10.8, p = 0.013) and non-depleted rats (5.4 g with 95% CI 1.2 to 9.6, p = 0.018) with plantar incision compared to vehicle treated rats. Despite a persistent reduction in mechanical hypersensitivity, clenbuterol did not alter the slope of recovery when modeled over several days (p = 0.053) or five weeks in depleted rats (p = 0.64). Systemic clenbuterol suppressed the enhanced microglial activation in depleted rats and reduced the density of macrophage at the site of incision. Direct spinal infusion of clenbuterol failed to reduce mechanical hypersensitivity in depleted rats with incision suggesting that beneficial effects of ß2-AR stimulation in this model are largely peripherally mediated. Lastly, we examined ß2-AR distribution in the spinal cord and skin using in-situ hybridization and IHC. These data add to our understanding of the role of ß2-ARs in the nervous system on hypersensitivity after surgical incision and extend previously observed anti-inflammatory actions of ß2-AR agonists to models of surgical injury.

2.
Anesthesiology ; 134(2): 283-344, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33372949

RESUMO

The authors provide a comprehensive summary of all randomized, controlled trials (n = 76) involving the clinical administration of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, USA) to control postoperative pain that are currently published. When infiltrated surgically and compared with unencapsulated bupivacaine or ropivacaine, only 11% of trials (4 of 36) reported a clinically relevant and statistically significant improvement in the primary outcome favoring liposomal bupivacaine. Ninety-two percent of trials (11 of 12) suggested a peripheral nerve block with unencapsulated bupivacaine provides superior analgesia to infiltrated liposomal bupivacaine. Results were mixed for the 16 trials comparing liposomal and unencapsulated bupivacaine, both within peripheral nerve blocks. Overall, of the trials deemed at high risk for bias, 84% (16 of 19) reported statistically significant differences for their primary outcome measure(s) compared with only 14% (4 of 28) of those with a low risk of bias. The preponderance of evidence fails to support the routine use of liposomal bupivacaine over standard local anesthetics.


Assuntos
Anestésicos Locais/uso terapêutico , Bupivacaína/uso terapêutico , Bloqueio Nervoso/métodos , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Humanos , Lipossomos/administração & dosagem , Nervos Periféricos/efeitos dos fármacos , Resultado do Tratamento
3.
Pain Med ; 21(Suppl 2): S53-S61, 2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33313729

RESUMO

BACKGROUND: Percutaneous peripheral nerve stimulation (PNS) is an analgesic modality involving the insertion of a lead through an introducer needle followed by the delivery of electric current after needle withdrawal. This modality has been used extensively to treat chronic pain, but only small series have been published involving postoperative pain. The ultimate objective of this study is to determine the postoperative effects of percutaneous PNS following moderately to severely painful ambulatory surgery within a real-world clinical practice setting. The primary hypothesis is that surgical pain and opioid consumption during the initial 7 days after surgery will be reduced by percutaneous PNS compared with usual and customary analgesia (dual primary outcome measures). DESIGN: A multicenter pragmatic effectiveness trial. We are randomizing participants having painful orthopedic surgical procedures of the upper and lower extremity to receive 14 days of either 1) electrical stimulation or 2) sham in a double-masked fashion. End points are being assessed at various time points over 12 postoperative months. SUMMARY: The postoperative experience will be much improved if percutaneous PNS provides potent analgesia while concurrently decreasing opioid requirements following painful surgery. Because this modality can be administered for up to 60 days at home, it may provide postoperative analgesia that outlasts surgical pain yet has relatively few risks and, unlike opioids, has no systemic side effects or potential for abuse, addiction, and overdose. Percutaneous PNS has the potential to revolutionize postoperative analgesia as it has been practiced for the past century. This study will inform key stakeholders regarding an evidence-based nonpharmacologic approach to the management of postoperative pain.

4.
Pain ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33021563

RESUMO

Phantom limb pain is thought to be sustained by reentrant neural pathways which provoke dysfunctional reorganization in the somatosensory cortex. We hypothesized that disrupting reentrant pathways with a 6-day-long continuous peripheral nerve block reduces phantom pain 4 weeks after treatment. We enrolled patients who had an upper- or lower-limb amputation and established phantom pain. Each was randomized to receive a 6-day perineural infusion of either ropivacaine or normal saline. The primary outcome was the average phantom pain severity as measured with a Numeric Rating Scale (0-10) at 4 weeks, after which an optional crossover treatment was offered within the following 0-12 weeks. Pretreatment pain scores were similar in both groups, with a median [interquartile range] of 5.0 [4.0, 7.0] for each. After 4 weeks, average phantom limb pain intensity was a mean (SD) of 3.0 (2.9) in patients given local anesthetic versus 4.5 (2.6) in those given placebo (difference (95% CI) 1.3 (0.4, 2.2), P=0.003). Patients given local anesthetic had improved global impression of change and less pain-induced physical and emotional dysfunction, but did not differ on depression scores. For subjects who received only the first infusion (no self-selected crossover), the median decrease in phantom limb pain at 6 months for treated subjects was 3.0 [0, 5.0] vs. 1.5 [0, 5.0] for the placebo group; there appeared to be little residual benefit at 12 months. We conclude that a 6-day continuous peripheral nerve block reduces phantom limb pain as well as physical and emotional dysfunction for at least 1 month.

6.
Pain ; 161(5): 949-959, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32040074

RESUMO

Pain and hypersensitivity months after peripheral injury reflect abnormal input from peripheral afferents likely in conjunction with central sensitization. We hypothesize that peripheral changes occur in defined sensory afferents and resolve as behavioral response to injury resolves. Male Sprague-Dawley rats underwent sham or partial L5 spinal nerve ligation, and paw withdrawal threshold (PWT) was sequentially measured during recovery. At 2, 4, 8, and 12 weeks after injury, randomized animals underwent electrophysiologic assessment of L4 fast-conducting high- and low-threshold mechanoreceptors, and individual neuronal mechanical thresholds (MTs) were contrasted with PWTs in the same animals. Paw withdrawal thresholds decreased after injury and resolved over time (P < 0.001). Similarly, MTs of fast-conducting high-threshold mechanoreceptors decreased after injury and resolved over time (P < 0.001). By contrast, MTs of low-threshold mechanoreceptors increased after injury and resolved over time (P < 0.001). Distributions of recordings from each afferent subtype were perturbed after injury, and this too resolved over time. After resolution of behavioral changes, several electrical abnormalities persisted in both neuronal subtypes. These data extend previous findings that mechanically sensitive nociceptors are sensitized, whereas tactile, largely Aß afferents are desensitized after nerve injury by showing that the time course of resolution of these changes mirrors that of behavioral hypersensitivity in a surgical injury including neural damage. These data support a role of abnormal peripheral input, from both nociceptor and tactile afferents, during recovery from peripheral injury and underscore the potential importance of both classes of afferents as potential targets for pain treatment.

7.
Pain ; 161(5): 960-969, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32040075

RESUMO

Pain alters cognitive performance through centrally mediated effects in the brain. In this study, we hypothesized that persistent activation of peripheral nociceptors after injury would lead to the development of a chronic pain state that impairs attention-related behavior and results in changes in peripheral neuron phenotypes. Attentional performance was measured in rats using the 5-choice serial reaction time titration variant to determine the initial impact of partial L5 spinal nerve ligation and the effect of persistent nociceptor activation on the resolution of injury. The changes in peripheral neuronal sensibilities and phenotypes were determined in sensory afferents using electrophysiologic signatures and receptive field properties from dorsal root ganglion recordings. Partial spinal nerve injury impaired attentional performance, and this was further impaired in a graded fashion by nociceptive input through an engineered surface. Impairment in attention persisted for only up to 4 days initially, followed by a second phase 7 to 10 weeks after injury in animals exposed to nociceptive input. In animals with prolonged impairment in behavior, the mechanonociceptors displayed a persistent hypersensitivity marked by decreased threshold, increased activity to a given stimulus, and spontaneous activity. Nerve injury disrupts attentional performance acutely and is worsened with peripheral mechanonociceptor activation. Acute impairment resolves, but persistent nociceptive activation produces re-emergence of impairment in the attention-related task associated with electrophysiological abnormalities in peripheral nociceptors. This is consistent with the development of a chronic pain state marked by cognitive impairment and related to persistently abnormal peripheral input.

8.
J Physiol Sci ; 69(5): 769-777, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31267368

RESUMO

Operant methods that allow animals to avoid painful stimuli are interpreted to assess the aversive quality of pain; however, such measurements require investigator-initiated stimuli to animals. Here we developed a shuttle maze test to repeatedly assess activity associated nociception without forced stimulation. Rats ambulate back and forth between two treat feeders by taking either a short route with a prickly surfaced arch or a longer route with a smooth floor. L5-L6 spinal nerve ligation (SNL) reduced the preference for the short route with the arch, correlated with hypersensitivity in the hind paw. Oral gabapentin restored the short route preference and reduced hypersensitivity in SNL rats, and blockade of spinal α2-adrenoceptors reduced gabapentin's effects on hypersensitivity but not on preference index. These results suggest that SNL injury alters behavior in the shuttle maze test and that the shuttle maze test shows comparable results to reflexive hypersensitivity after SNL in magnitude and response to gabapentin.


Assuntos
Comportamento de Escolha/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Animais , Modelos Animais de Doenças , Alimentos , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Ligadura/métodos , Masculino , Neuralgia/metabolismo , Neuralgia/fisiopatologia , Limiar da Dor/fisiologia , Ratos , Ratos Sprague-Dawley , Nervos Espinhais/metabolismo , Nervos Espinhais/fisiopatologia , Ácido gama-Aminobutírico/metabolismo
9.
Pain ; 160(10): 2350-2357, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31145215

RESUMO

Pain and physical activity are tightly intertwined. Although their relationship has been explored in chronic pain conditions, we know little about the pattern of recovery in activity and its short- and long-term relationship with pain after surgery. We recruited 103 women undergoing elective cesarean delivery and acquired daily pain assessments and hourly steps in 98 of them for 2 months after surgery. Compliance was good, with 78% of subjects missing less than 7 days of activity. Study personnel required daily checking for compliance and 20 minutes per subject per week in study. Activity increased over the first 2 postoperative months in a log(time) manner. The slope of each modeled individual curve for activity was inversely correlated (r = -0.54; P < 0.0001) with worst daily pain. After removing these 2-month trends, pain and activity within an individual day were negatively associated with each point increase in pain being inversely associated with -119 steps (95% confidence interval [CI] = -214 to -25; P = 0.013). A patient's previous experience of pain was not associated with current activity as well as current activity was not associated with future pain scores. These data, although limited by the study of a single operation in a unique social circumstance with low risk of chronic postsurgical pain, demonstrate feasibility of measuring hourly activity for 2 months after surgery. Recovery from pain and inactivity are tightly correlated, and the negative relationship between within-day pain and activity without interday carryover relationships is in stark contrast to findings in chronic pain conditions.


Assuntos
Acelerometria/métodos , Cesárea/efeitos adversos , Exercício Físico/fisiologia , Medição da Dor/métodos , Dor Pós-Operatória/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Acelerometria/psicologia , Adulto , Cesárea/psicologia , Cesárea/tendências , Exercício Físico/psicologia , Estudos de Viabilidade , Feminino , Humanos , Medição da Dor/psicologia , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/psicologia , Gravidez , Estudos Prospectivos
10.
Mol Pain ; 15: 1744806919845750, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31012376

RESUMO

Since the failure of specific substance P antagonists to induce analgesia, the role of tachykinins in the development of neuropathic pain states has been discounted. This conclusion was reached without studies on the role of tachykinins in normal patterns of primary afferents response and sensitization or the consequences of their absence on the modulation of primary mechanonociceptive afferents after injury. Nociceptive afferents from animals lacking tachykinins (Tac1 knockout) showed a disrupted pattern of activation to tonic suprathreshold mechanical stimulation. These nociceptors failed to encode the duration and magnitude of natural pronociceptive stimuli or to develop mechanical sensitization as consequence of this stimulation. Moreover, paw edema, hypersensitivity, and weight bearing were also reduced in Tac1 knockout mice 24 h after paw incision surgery. At this time, nociceptive afferents from these animals did not show the normal sensitization to mechanical stimulation or altered membrane electrical hyperexcitability as observed in wild-type animals. These changes occurred despite a similar increase in calcitonin gene-related peptide immunoreactivity in sensory neurons in Tac1 knockout and normal mice. Based on these observations, we conclude that tachykinins are critical modulators of primary nociceptive afferents, with a preeminent role in the electrical control of their excitability with sustained activation or injury.


Assuntos
Nociceptividade , Células Receptoras Sensoriais/metabolismo , Taquicininas/metabolismo , Animais , Peptídeo Relacionado com Gene de Calcitonina , Estimulação Elétrica , Fenômenos Eletrofisiológicos , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Vértebras Lombares/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Substância P , Canais de Cátion TRPV/metabolismo
11.
Pain ; 160(5): 1146-1155, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30920428

RESUMO

Oxytocin reduces primary sensory afferent excitability and produces analgesia in part through a peripheral mechanism, yet its actions on physiologically characterized, mechanically sensitive afferents in normal and neuropathic conditions are unknown. We recorded intracellularly from L4 dorsal root ganglion neurons characterized as low-threshold mechanoreceptors (LTMRs) or high-threshold mechanoreceptors (HTMRs) in female rats 1 week after L5 partial spinal nerve injury or sham control (n = 24 rats/group) before, during, and after ganglionic perfusion with oxytocin, 1 nM. Nerve injury desensitized and hyperpolarized LTMRs (membrane potential [Em] was -63 ± 1.8 mV in sham vs -76 ± 1.4 mV in nerve injury; P < 0.001), and sensitized HTMRs without affecting Em. In nerve-injured rats, oxytocin depolarized LTMRs towards normal (Em = -69 ± 1.9 mV) and, in 6 of 21 neurons, resulted in spontaneous action potentials. By contrast, oxytocin hyperpolarized HTMRs (Em = -68 ± 2.7 mV before vs -80 ± 3.2 mV during oxytocin exposure; P < 0.01). These effects were reversed after removal of oxytocin, and oxytocin had minimal effects in neurons from sham surgery animals. Sensory afferent neurons immunopositive for the vasopressin 1a receptor were larger (34 ± 6.3 µm, range 16-57 µm) than immunonegative neurons (26 ± 3.4 µm, range 15-43 µm; P < 0.005). These data replicate findings that neuropathic injury desensitizes LTMRs while sensitizing HTMRs and show rapid and divergent oxytocin effects on these afferent subtypes towards normal, potentially rebalancing input to the central nervous system. Vasopressin 1a receptors are present on medium to large diameter afferent neurons and could represent oxytocin's target.


Assuntos
Gânglios Espinais/patologia , Nociceptores/efeitos dos fármacos , Ocitocina/uso terapêutico , Traumatismos dos Nervos Periféricos/patologia , Células Receptoras Sensoriais/efeitos dos fármacos , Tato , Potenciais de Ação/efeitos dos fármacos , Vias Aferentes/fisiopatologia , Animais , Modelos Animais de Doenças , Estimulação Elétrica , Feminino , Mecanorreceptores/efeitos dos fármacos , Nociceptores/fisiologia , Ocitocina/farmacologia , Limiar da Dor/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptores de Vasopressinas/metabolismo , Células Receptoras Sensoriais/fisiologia
13.
Pain Rep ; 4(3): e621, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28989992

RESUMO

INTRODUCTION: Randomized clinical trials (RCTs) are considered the gold standard when assessing the efficacy of interventions because randomization of treatment assignment minimizes bias in treatment effect estimates. However, if RCTs are not performed with methodological rigor, many opportunities for bias in treatment effect estimates remain. Clear and transparent reporting of RCTs is essential to allow the reader to consider the opportunities for bias when critically evaluating the results. To promote such transparent reporting, the Consolidated Standards of Reporting Trials (CONSORT) group has published a series of recommendations starting in 1996. However, a decade after the publication of the first CONSORT guidelines, systematic reviews of clinical trials in the pain field identified a number of common deficiencies in reporting (e.g., failure to identify primary outcome measures and analyses, indicate clearly the numbers of participants who completed the trial and were included in the analyses, or report harms adequately). METHODS: Qualitative review of a diverse set of published recommendations and systematic reviews that addressed the reporting of clinical trials, including those related to all therapeutic indications (e.g., CONSORT) and those specific to pain clinical trials. RESULTS: A checklist designed to supplement the content covered in the CONSORT checklist with added details relating to challenges specific to pain trials or found to be poorly reported in recent pain trials was developed. CONCLUSIONS: Authors and reviewers of analgesic RCTs should consult the CONSORT guidelines and this checklist to ensure that the issues most pertinent to pain RCTs are reported with transparency.

14.
Adv Exp Med Biol ; 1099: 93-100, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30306517

RESUMO

Gabapentinoids are effective in a wide range of animal pain models and in patients with neuropathic pain and has become one of first-line treatments for neuropathic pain. Because spinal plasticity and sensitization have been intensely studied in neuropathic pain, most laboratory studies have focused on actions of gabapentinoids in the spinal cord, where they reduce primary afferent traffic and excitation of spinal nociceptive neurons, via interaction with α2δ subunits of voltage-gated Ca2+ channels. However, a recent clinical study questioned the relevance of this in vitro and in vivo rodent studies by demonstrating a complete lack of clinical efficacy of intrathecal gabapentin in patients with chronic pain. Curiously, preclinical studies continue to focus on spinal cord actions of gabapentinoids despite this lack of translation to humans.We and others demonstrated that gabapentin inhibits presynaptic GABA release and induces glutamate release from astrocytes in the locus coeruleus (LC), thereby increasing LC neuron activity and spinal noradrenaline release, and that gabapentin relies on this action in the LC for its analgesia. We also recently discovered that, with prolonged time after neuropathic injury, noradrenergic neurons in the LC become less responsive to gabapentin, leading to impaired gabapentin analgesia, and that astroglial glutamate dysregulation is critical to this impaired LC response. The clinically available drug valproate increases glutamate transporter-1 (GLT-1) expression in the LC to restore this impaired gabapentin analgesia.


Assuntos
Analgesia , Gabapentina/farmacologia , Locus Cerúleo/fisiologia , Neuralgia/tratamento farmacológico , Norepinefrina/fisiologia , Animais , Transportador 2 de Aminoácido Excitatório/fisiologia , Ácido Glutâmico/fisiologia , Humanos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Ácido gama-Aminobutírico
16.
Anesthesiology ; 129(4): 778-790, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29952818

RESUMO

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Cognitive capacity may be reduced from inflammation, surgery, anesthesia, and pain. In this study, we hypothesized that incision-induced nociceptive input impairs attentional performance and alters neuronal activity in the prefrontal cortex. METHODS: Attentional performance was measured in rats by using the titration variant of the 5-choice serial reaction time to determine the effect of surgical incision and anesthesia in a visual attention task. Neuronal activity (single spike and local field potentials) was measured in the medial prefrontal cortex in animals during the task. RESULTS: Incision significantly impaired attention postoperatively (area under curve of median cue duration-time 97.2 ± 56.8 [n = 9] vs. anesthesia control 25.5 ± 14.5 s-days [n = 9], P = 0.002; effect size, η = 0.456). Morphine (1 mg/kg) reduced impairment after incision (area under curve of median cue duration-time 31.6 ± 36.7 [n = 11] vs. saline 110 ± 64.7 s-days [n = 10], P < 0.001; η = 0.378). Incision also decreased cell activity (n = 24; 1.48 ± 0.58 vs. control, 2.93 ± 2.02 bursts/min; P = 0.002; η = 0.098) and local field potentials (n = 28; η = 0.111) in the medial prefrontal cortex. CONCLUSIONS: These results show that acute postoperative nociceptive input from incision reduces attention-related task performance and decreases neuronal activity in the medial prefrontal cortex. Decreased neuronal activity suggests nociceptive input is more than just a distraction because neuronal activity increases during audiovisual distraction with similar behavioral impairment. This suggests that nociceptive input and the medial prefrontal cortex may contribute to attentional impairment and mild cognitive dysfunction postoperatively. In this regard, pain may affect postoperative recovery and return to normal activities through attentional impairment by contributing to lapses in concentration for routine and complex tasks.


Assuntos
Atenção/fisiologia , Neurônios/fisiologia , Medição da Dor/métodos , Córtex Pré-Frontal/fisiologia , Tempo de Reação/fisiologia , Ferida Cirúrgica/fisiopatologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Analgésicos Opioides/farmacologia , Analgésicos Opioides/uso terapêutico , Animais , Atenção/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Medição da Dor/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Tempo de Reação/efeitos dos fármacos , Ferida Cirúrgica/tratamento farmacológico
17.
Pain ; 159(10): 2088-2096, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29905650

RESUMO

We know very little about the change in pain in the first 2 months after surgery. To address this gap, we studied 530 women scheduled for elective cesarean delivery who completed daily pain diaries for 2 months after surgery through text messaging. Over 82% of subjects missed fewer than 10 diary entries and were included in the analysis. Completers were more likely to be Caucasian, nonsmokers, and with fewer previous pregnancies than noncompleters. Daily worst pain intensity ratings for the previous 24 hours were fit to a log(time) function and allowed to change to a different function up to 3 times according to a Bayesian criterion. All women had at least one change point, occurring 22 ± 9 days postoperatively, and 81% of women had only one change, most commonly to a linear function at 0 pain. Approximately 9% of women were predicted to have pain 2 months after surgery, similar to previous observations. Cluster analysis revealed 6 trajectories of recovery from pain. Predictors of cluster membership included severity of acute pain, perceived stress, surgical factors, and smoking status. These data demonstrate feasibility but considerable challenges to this approach to data acquisition. The form of the initial process of recovery from pain is common to all women, with divergence of patterns at 2 to 4 weeks after cesarean delivery. The change-point model accurately predicts recovery from pain; its parameters can be used to assess predictors of speed of recovery; and it may be useful for future observational, forecasting, and interventional trials.


Assuntos
Cesárea/efeitos adversos , Dor Pós-Operatória/etiologia , Recuperação de Função Fisiológica/fisiologia , Adulto , Teorema de Bayes , Cultura , Feminino , Humanos , Medição da Dor , Alta do Paciente , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto Jovem
18.
Anesthesiology ; 129(3): 544-556, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29912007

RESUMO

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Recovery from pain after surgery is faster after cesarean delivery than after other abdominal procedures. The authors hypothesized that recovery in rats after surgery could be reversed by antagonism of spinal oxytocin or vasopressin receptors, that there may be a sex difference, and that spinal oxytocin innervation could change after surgery. METHODS: Male and female rats underwent partial spinal nerve ligation surgery. Effects of nonselective and selective oxytocin and vasopressin 1A receptor antagonists on mechanical hypersensitivity during partial recovery were assessed (n = 8 to 14/group). Oxytocin immunoreactivity in the dorsal horn of the spinal cord (n = 7 to 8/group) and messenger RNA (mRNA) expression for oxytocin-binding receptors in dorsal root ganglia and spinal cord (n = 8/group) were measured. RESULTS: Intrathecal injection of oxytocin and vasopressin receptor antagonists were similarly effective at reducing withdrawal threshold (in all experiments from 22 [19, 26] median [first quartile, third quartile]) g to 8.3 [6.4, 12] g after injection) in both sexes, while having no or minimal effects in animals without surgery. Oxytocin fiber immunoreactivity was 3- to 5-fold greater in lumbar than other regions of the spinal cord and was increased more than 2-fold in lumbar cord ipsilateral to surgery. Injury was also associated with a 6.5-fold increase in oxytocin receptor and a 2-fold increase in vasopressin 1A receptor messenger RNA expression in the L4 dorsal root ganglion ipsilateral to surgery. CONCLUSIONS: These findings suggest that the capacity for oxytocin signaling in the spinal cord increases after surgery and that spinal oxytocin signaling plays ongoing roles in both sexes in recovery from mechanical hypersensitivity after surgery with known nerve injury.


Assuntos
Receptores de Ocitocina/fisiologia , Receptores de Vasopressinas/fisiologia , Recuperação de Função Fisiológica/fisiologia , Transdução de Sinais/fisiologia , Nervos Espinhais/lesões , Nervos Espinhais/cirurgia , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos/farmacologia , Feminino , Hiperalgesia/etiologia , Hiperalgesia/prevenção & controle , Injeções Espinhais , Ligadura , Masculino , Ocitocina/antagonistas & inibidores , Ocitocina/fisiologia , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Ratos , Ratos Sprague-Dawley , Receptores de Ocitocina/antagonistas & inibidores , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Nervos Espinhais/efeitos dos fármacos
20.
J Clin Sleep Med ; 14(4): 549-555, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29609706

RESUMO

STUDY OBJECTIVES: To measure prevalence and severity of third trimester obstructive sleep apnea and evaluate postpartum resolution. To assess a novel biomarker for screening for obstructive sleep apnea in pregnancy. METHODS: This prospective observational study was performed at Wake Forest School of Medicine obstetrics clinics between April 2014 and December 2015. Fractional exhaled nitric oxide measurements and sleep studies were obtained and compared at 32 0/7 to 35 6/7 weeks gestation and postpartum. Exhaled nitric oxide and risk factors for the development of gestational sleep apnea were evaluated for predictive ability independently and in screening models. RESULTS: Of 76 women enrolled, 73 performed valid sleep studies in pregnancy and 65 had an additional valid study 6 to 15 weeks postpartum. Twenty-four women (37%) had gestational sleep apnea compared with 23 (35%) with postpartum sleep apnea (P > .99). Eight of 11 women (73%) retested 6 to 8 months postpartum had persistent sleep apnea. Exhaled nitric oxide had moderate discrimination screening for sleep apnea in pregnancy (area under the receiver operating characteristic curve = 0.64). A model utilizing exhaled nitric oxide, pregnancy-specific screening, and Mallampati score improved ability to identify women at risk for gestational sleep apnea (sensitivity = 46%, specificity = 91% and likelihood ratio = 5.11, area under receiver operating characteristic curve = 0.75). CONCLUSIONS: Obstructive sleep apnea is common in the early postpartum period and often persisted at least 6 months. Exhaled nitric oxide as a sole biomarker to screen for sleep apnea in pregnancy has only modest discrimination. Combined with additional parameters sensitivity and specificity improved. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, Identifier: NCT02100943, Title: Exhaled Nitric Oxide as a Biomarker of Gestational Obstructive Sleep Apnea and Persistence Postpartum, URL: https://clinicaltrials.gov/ct2/show/NCT02100943.


Assuntos
Complicações na Gravidez/diagnóstico , Apneia Obstrutiva do Sono/complicações , Adulto , Biomarcadores/análise , Testes Respiratórios , Feminino , Humanos , Óxido Nítrico/análise , Período Pós-Parto , Gravidez , Complicações na Gravidez/epidemiologia , Terceiro Trimestre da Gravidez , Prevalência , Estudos Prospectivos , Fatores de Risco , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia
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