Behavioral Pain Responses Research Articles

Effect of Vibration on Pain Response to Heel Lance: A Pilot Randomized Control Trial.

Applied mechanical vibration in pediatric and adult populations has been shown to be an effective analgesic for acute and chronic pain, including needle pain. Studies among the neonatal population are lacking. According to the Gate Control Theory, it is expected that applied mechanical vibration will have a summative effect with standard nonpharmacologic pain control strategies, reducing behavioral and physiologic pain responses to heel lancing. To determine the safety and efficacy of mechanical vibration for relief of heel lance pain among neonates. In this parallel design randomized controlled trial, eligible enrolled term or term-corrected neonates (n = 56) in a level IV neonatal intensive care unit were randomized to receive either sucrose and swaddling or sucrose, swaddling, and vibration for heel lance analgesia. Vibration was applied using a handheld battery-powered vibrator (Norco MiniVibrator, Hz = 92) to the lateral aspect of the lower leg along the sural dermatome throughout the heel lance procedure. Neonatal Pain, Agitation, and Sedation Scale (N-PASS) scores, heart rate, and oxygen saturations were collected at defined intervals surrounding heel lancing. Infants in the vibration group (n = 30) had significantly lower N-PASS scores and more stable heart rates during heel stick (P = .006, P = .037) and 2 minutes after heel lance (P = .002, P = .016) than those in the nonvibration group. There were no adverse behavioral or physiologic responses to applied vibration in the sample. Applied mechanical vibration is a safe and effective method for managing heel lance pain. This pilot study suggests that mechanical vibration warrants further exploration as a nonpharmacologic pain management tool among the neonatal population.

Amygdala-mediated mechanisms regulate visceral hypersensitivity in adult females following early life stress: importance of the glucocorticoid receptor and corticotropin-releasing factor.

Alterations in amygdala activity are apparent in women who report a history of early life stress (ELS) and those diagnosed with chronic pain disorders. Chronic stress in adulthood induces visceral hypersensitivity by alterations in glucocorticoid receptor (GR) and corticotropin-releasing factor (CRF) expression within the central amygdala (CeA). Here, we hypothesized that unpredictable ELS, previously shown to induce visceral hypersensitivity in adult female rats, alters GR and CRF expression in the CeA. After neonatal ELS, visceral sensitivity and GR and CRF gene expression were quantified in adult female rats. After unpredictable ELS, adult female rats exhibited visceral hypersensitivity and increased expression of GR and CRF in the CeA. After predictable ELS, adult female rats demonstrated normosensitive behavioral pain responses and upregulation of GR but not CRF in the CeA. After the ELS paradigms, visceral sensitivity and gene expression within the CeA were unaffected in adult male rats. The role of GR and CRF in modulating visceral sensitivity in adult female rats after ELS was investigated using oligodeoxynucleotide sequences targeted to the CeA for knockdown of GR or CRF. Knockdown of GR increased visceral sensitivity in all rats but revealed an exaggerated visceral hypersensitivity in females with a history of predictable or unpredictable ELS compared with that of controls. Knockdown of CRF expression or antagonism of CRF1R in the CeA attenuated visceral hypersensitivity after unpredictable ELS. This study highlights a shift in GR and CRF regulation within the CeA after ELS that underlies the development of visceral hypersensitivity in adulthood.

Breastfeeding for procedural pain in infants beyond the neonatal period.

Breastfeeding for procedural pain in infants beyond the neonatal period.

Effect of early procedural pain experience on subsequent pain responses among premature infants

Background and objectivesPreterm newborns are exposed to repeated procedural pain during their NICU stay. Acute pain has negative short-term effects and may have adverse neurodevelopmental sequelae. Disagreement among researchers exists in the direction of pain responses. We aimed at evaluating the short-term effects of early procedural pain exposure on subsequent behavioral and physiological responses among preterm infants; and to define possible contributing factors. Patients and methodsA prospective study included 203 preterm newborns recruited from 2 community centers, excluding cases having conditions that may affect pain responses. They were categorized into: group I including cases who were exposed to painful procedures; and group II were not exposed. Pain response to heel-stick procedure was assessed by Neonatal Infant Pain Scale to measure behavioral response, and changes in heart rate and oxygen saturation to evaluate physiological responses. ResultsHistory of pain exposure and number of procedures were the only independent variables that predicted subsequent pain responses while other contextual factors had no significant impact. The behavioral pain responses were blunted in group I with lower pain scores during and after the heel-stick test, while physiological responses were exaggerated with a higher heart rate and oxygen saturation variability. ConclusionOn studying the physiological and behavioral responses to pain in the premature infants, it was found that prior pain exposure and the number of procedures predict dampened behavioral and exaggerated physiologic subsequent pain responses. Protocols for minimization of pain exposure and pain control need to be implemented to avoid infant distress and long-term neurodevelopmental sequelae.

Evaluating the effects of recombinant human bone morphogenetic protein-2 on pain-associated behaviors in a rat model following implantation near the sciatic nerve.

OBJECTIVE It has been hypothesized that the recombinant human bone morphogenetic protein-2 (rhBMP-2) amplification of the host inflammatory response interacts with nerves in the spine and contributes to the occurrence of new, postoperative complaints of radiculitis. This in vivo rat study was conducted to assess the capacity for rhBMP-2/ACS (rhBMP-2 applied to absorbable collagen sponge [ACS]) to stimulate pain-associated behaviors in the rat chronic constriction injury (CCI) model. METHODS Rats were randomly assigned to one of 14 treatment groups. Half of the animals underwent a sham procedure in which the left sciatic nerve was exposed and manipulated but no ligature was placed (Sham cohort), while the remaining animals had chromic gut sutures tied around the sciatic nerve to induce CCI (CCI cohort). The following test articles were applied to the sciatic nerve in each cohort: saline alone, saline applied to ACS, 0.1 mg/ml rhBMP-2 applied to ACS, or 1.0 mg/ml rhBMP-2 applied to ACS. The ACS was either wrapped around the sciatic nerve or implanted adjacent to the nerve. Thermal withdrawal latency was assessed on Days 7, 14, 21, and 28 postoperatively. Isolated nerves from selected rats in each group were examined and assessed for histopathological changes on Days 3, 7, 14, and 28. RESULTS CCI produced a significant pain behavioral response for all treatment groups at all time points. In the Sham cohort, 0.1 mg/ml rhBMP-2/ACS wrapped around the nerve (WRP) decreased thermal withdrawal on Day 28, and 1.0 mg/ml rhBMP-2/ACS placed adjacent to the nerve (ADJ) decreased thermal withdrawal on Days 21 and 28. Conversely, in the CCI cohort, 0.1 mg/ml rhBMP-2/ACS ADJ increased thermal withdrawal latencies on Day 7; 1.0 mg/ml rhBMP-2/ACS ADJ increased thermal withdrawal latencies on Day 7; and 1.0 mg/ml rhBMP-2/ACS WRP increased thermal withdrawal on Days 7 and 14. Histologically, the effect of rhBMP-2 on nerve inflammation was unclear, as inflammatory cell infiltration was similar in the rhBMP-2/ACS and saline/ACS groups. rhBMP-2 was variably associated with bone formation within the epineurium at 14 days, and more prevalently at 28 days, with no clear relationship between dose or ACS positioning. CONCLUSIONS In this study, rhBMP-2/ACS did not appear to induce pain independent of grossly visible ectopic bone formation. At the earliest time points, rhBMP-2 appeared to have a neuroprotective effect as evidenced by decreased pain exhibited by the rhBMP-2-treated animals in the CCI cohort, but this effect diminished over time, and by Day 28, the pain behavioral responses in the rhBMP-2-treated group were comparable to those in the group in which saline was applied to the nerve. In the Sham cohort, there was a dose-independent induction of pain at later time points, presumably due to new bone formation mechanically irritating the nerve. Histological examination revealed nerve lesions that appeared to be caused by mechanical trauma associated with surgical manipulation of the nerve during placement of the ACS and/or CCI sutures.

Mindfulness-Meditation-Based Pain Relief Is Not Mediated by Endogenous Opioids.

Endogenous opioids have been repeatedly shown to be involved in the cognitive inhibition of pain. Mindfulness meditation, a practice premised on directing nonjudgmental attention to arising sensory events, reduces pain by engaging mechanisms supporting the cognitive control of pain. However, it remains unknown if mindfulness-meditation-based analgesia is mediated by opioids, an important consideration for using meditation to treat chronic pain. To address this question, the present study examined pain reports during meditation in response to noxious heat and administration of the opioid antagonist naloxone and placebo saline. The results demonstrate that meditation-based pain relief does not require endogenous opioids. Therefore, the treatment of chronic pain may be more effective with meditation due to a lack of cross-tolerance with opiate-based medications.

Effects of Saffron (Crocus sativus L.) Stigma Extract and its Active Constituent Crocin on Neuropathic Pain Responses in a Rat Model of Chronic Constriction Injury.

This study was designed to investigate the therapeutic effects of saffron (Crocus sativus L.) and its main constituent crocin on neuropathic pain behavioral responses induced by chronic constriction injury (CCI) in rats. Adult male Wistar rats (200 to 250 g) were randomly assigned into 5 groups: Sham + saline, CCI + saline, CCI+ saffron (30 mg/kg), CCI + crocin (15 mg/kg) and CCI + crocin (30 mg/kg). CCI was induced by applying 4 loose ligatures around the sciatic nerve. Two weeks after nerve lesion, injections of saline, saffron or crocin were started and continued until 26(th) day post-surgery. Pain behavioral responses including mechanical allodynia (von Frey filament testing) and thermal hyperalgesia were measured in 14, 17, 20, 23, 26, and 40(th) days after CCI. CCI significantly increased pain behavioral responses. Saffron and crocin (30 mg/kg) decreased thermal hyperalgesia and mechanical allodynia on day 26, and this effect continued until the day 40. Crocin at lower dose (15 mg/kg) was ineffective. These findings indicate that treatment of saffron and crocin after CCI may have a therapeutic effect against neuropathic pain, suggesting that these substances may offer new strategies for the treatment of this highly debilitating condition.

Effects of music therapy on pain responses induced by blood sampling in premature infants: A randomized cross-over trial

Background:Premature infants are subjected to many painful procedures during care and treatment. The aim of this study was to assess the effect of music therapy on physiological and behavioral pain responses of premature infants during and after blood sampling.Materials and Methods:This study was a cross-over clinical trial conducted on 20 infants in a hospital affiliated to Tehran University of Medical Sciences for a 5-month period in 2011. In the experimental group, Transitions music was played from 5 min before until 10 min after blood sampling. The infants’ facial expressions and physiological measures were recorded from 10 min before until 10 min after sampling. All steps and measurements, except music therapy, were the same for the control group. Data were analyzed using SAS and SPSS software through analysis of variance (ANOVA) and Chi-square tests.Results:There were significant differences between the experimental and control groups (P = 0.022) in terms of heart rate during needle extraction and at the first 5 min after sampling (P = 0.005). Considering the infant's sleep–wake state in the second 5 min before sampling, the statistical difference was significant (P = 0.044). Difference was significant (P = 0.045) during injection of the needle, in the first 5 min after sampling (P = 0.002), and in the second 5 min after sampling (P = 0.005). There were significant difference in infants’ facial expressions of pain in the first 5 min after sampling (P = 0.001).Conclusions:Music therapy reduces the physiological and behavioral responses of pain during and after blood sampling.

Autonomic, Behavioral, and Subjective Pain Responses in Alzheimer's Disease.

To compare autonomic, behavioral, and subjective pain responses of patients with Alzheimer's disease (AD) to those of healthy seniors (HS). As few studies have examined patients with severe Alzheimer's disease (sAD), we emphasized inclusion of these patients together with mild/moderate Alzheimer's disease (mAD) patients to characterize pain responses potentially affected by disease severity. A controlled cross-sectional study involving repeated measures behavioral pain testing. An outpatient clinical setting and local nursing facilities. Community dwelling HS controls (N = 33) and individuals with chart-confirmed diagnoses of AD (N = 38, Diagnostic and Statistical Manual-IV criteria). HS and AD groups were compared in their responses to repeated applications of five pressure intensities (1-5 kg) on the distal forearm. Autonomic responses (heart rate [HR]), pain behaviors (vocal, facial, and bodily as scored by the Pain Assessment in Advanced Dementia [PAINAD] scale), and subjective pain ratings (Faces Pain Scale-Revised) were measured. HR responses to pressure stimuli were differentially affected based on AD severity: sAD patients had generally decreased HR reactivity compared with other groups (P < 0.01). In contrast, pain behaviors were increased in AD regardless of severity (P < 0.001), compared with HS, for all but the lowest pressure intensity. Increased behaviors occurred in all measured domains of the PAINAD (P < 0.005). While sAD were unreliable subjective reporters, mAD patients (N = 17) rated low level pressures as more painful than HS (P < 0.01). These findings provide behavioral and subjective-report evidence of increased acute pain sensitivity in AD, which should be taken into consideration with respect to pain management across the spectrum of AD severity.

Development of an Experimental Animal Model for Lower Back Pain by Percutaneous Injury-Induced Lumbar Facet Joint Osteoarthritis.

We report generation and characterization of pain-related behavior in a minimally invasive facet joint degeneration (FJD) animal model in rats. FJD was produced by a non-open percutaneous puncture-induced injury on the right lumbar FJs at three consecutive levels. Pressure hyperalgesia in the lower back was assessed by measuring the vocalization response to pressure from a force transducer. After hyperalgesia was established, pathological changes in lumbar FJs and alterations of intervertebral foramen size were assessed by histological and imaging analyses. To investigate treatment options for lumber FJ osteoarthritis-induced pain, animals with established hyperalgesia were administered with analgesic drugs, such as morphine, a selective COX-2 inhibitor, a non-steroidal anti-inflammatory drug (NSAID) (ketorolac), or pregabalin. Effects were assessed by behavioral pain responses. One week after percutaneous puncture-induced injury of the lumbar FJs, ipsilateral primary pressure hyperalgesia developed and was maintained for at least 12 weeks without foraminal stenosis. Animals showed decreased spontaneous activity, but no secondary hyperalgesia in the hind paws. Histopathological and microfocus X-ray computed tomography analyses demonstrated that the percutaneous puncture injury resulted in osteoarthritis-like structural changes in the FJs cartilage and subchondral bone. Pressure hyperalgesia was completely reversed by morphine. The administration of celecoxib produced moderate pain reduction with no statistical significance while the administration of ketorolac and pregabalin produced no analgesic effect on FJ osteoarthritis-induced back pain. Our animal model of non-open percutanous puncture-induced injury of the lumbar FJs in rats shows similar characteristics of low back pain produced by human facet arthropathy.

Does pain vary across the menstrual cycle? A review.

Reproductive hormones are implicated in moderating pain. Animal studies support both pronociceptive and antinociceptive actions of oestradiol and progesterone suggesting that the net effect of these hormones on pain is complex and likely depends on the interaction between hormones and the extent of fluctuation rather than absolute hormone levels. Several clinical pain conditions show variation in symptom severity across the menstrual cycle. Though, there is still no consensus on whether the menstrual cycle influences experimental pain sensitivity in healthy individuals. Comprehensive literature searches on clinical and experimental pain across the menstrual cycle, as well as gonadal hormones and pain were performed using the electronic databases PubMed, Google Scholar and the Cochrane Library. Full-text manuscripts were reviewed for relevancy and reference lists were cross-checked for additional relevant studies. Most of the more recent, well-controlled studies show that menstrual cycle phase has no effect on the perception of pain in healthy, pain-free women. Although recent studies investigating pain-related brain activation have shown differential activation patterns across the menstrual cycle in regions involved with cognitive and motor function, even in the absence of a behavioural pain response, suggesting that cognitive pain and bodily awareness systems are sensitive to menstrual cycle phase. The interaction between the gonadal hormones and pain perception is intricate and not entirely understood. We suggest further investigations on the association between female reproductive hormones and pain sensitivity by exploring the interaction between clinical and experimental pain and the hormone changes that characterize puberty, post-partum and the menopause transition.

Substance P and calcitonin gene related peptide mediate pain in chronic pancreatitis and their expression is driven by nerve growth factor.

Calcitonin gene-related peptide (CGRP), substance P and nerve growth factor play an important role in inflammatory pain in various somatic pain models but their role in chronic pancreatitis has not been well studied. The aim of this study was to investigate the effects of intrathecal administration of calcitonin gene-related peptide antagonist and substance P receptor antagonist on pain behavior in a rat model of chronic pancreatitis and to determine whether nerve growth factor drives the up-regulation of expression of these neuropeptides in sensory neurons. Pancreatitis was induced by retrograde infusion of trinitobenzene sulfonic acid into the pancreatic duct of adult rats. Three weeks post infusion continuous intrathecal infusion of the calcitonin gene-related peptide antagonist alpha CGRP8-37 or neurokinin-1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 was administered for seven days. The effects of treatment on pancreatic hyperalgesia were assessed by sensitivity of the abdominal wall to von Frey filament probing as well as by the nocifensive response to electrical stimulation of the pancreas. In a separate experiment chronic pancreatitis was induced and pancreas specific dorsal root ganglion neurons labeled with DiI were assessed for calcitonin gene-related peptide and substance P immunoreactivity. Intrathecal infusion of calcitonin gene-related peptide and neurokinin-1 receptor antagonists significantly attenuated behavioral pain responses in rats with chronic pancreatitis. Further, treatment of chronic pancreatitis rats with nerve growth factor antibody significantly reduced pancreas specific neurons expressing calcitonin gene-related peptide and substance P in thoracic dorsal root ganglion. Calcitonin gene-related peptide and substance P mediate pancreatic hyperalgesia in chronic pancreatitis and nerve growth factor in turn sustains the up-regulation of these neuropeptides in pancreatic sensory neurons.

Recruitment of hypothalamic orexin neurons after formalin injections in adult male rats exposed to a neonatal immune challenge.

Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in adulthood. In animal models, injections of the bacterial immune challenge, lipopolysaccharide (LPS), during the neonatal period has been shown to alter both neuroendocrine function and behavioral pain responses in adulthood. Interestingly, recent evidence suggests a role for the lateral hypothalamic peptide orexin in stress and nociceptive processing. However, whether neonatal LPS exposure affects the reactivity of the orexin system to formalin-induced inflammatory pain in later life remains to be determined. Male Wistar rats (n = 13) were exposed to either LPS or saline (0.05 mg/kg, i.p) on postnatal days (PND) 3 and 5. On PND 80–97, all rats were exposed to a subcutaneous hindpaw injection of 2.25% formalin. Following behavioral testing, animals were perfused and brains processed for Fos-protein and orexin immunohistochemistry. Rats treated with LPS during the neonatal period exhibited decreased licking behaviors during the interphase of the formalin test, the period typically associated with the active inhibition of pain, and increased grooming responses to formalin in adulthood. Interestingly, these behavioral changes were accompanied by an increase in the percentage of Fos-positive orexin cells in the dorsomedial and perifornical hypothalamus in LPS-exposed animals. Similar increases in Fos-protein were also observed in stress and pain sensitive brain regions that receive orexinergic inputs. These findings highlight a potential role for orexin in the behavioral responses to pain and provide further evidence that early life stress can prime the circuitry responsible for these responses in adulthood.

Contralateral Metabolic Activation Related to Plastic Changes in the Spinal Cord after Peripheral Nerve Injury in Rats

We have previously reported the crossed-withdrawal reflex in which the rats with nerve injury developed behavioral pain responses of the injured paw to stimuli applied to the contralateral uninjured paw. This reflex indicates that contralateral plastic changes may occur in the spinal cord after unilateral nerve injury. The present study was performed to elucidate the mechanisms and morphological correlates underlying the crossed-withdrawal reflex by using quantitative 14C-2-deoxyglucose (2-DG) autoradiography which can examine metabolic activities and spatial patterns simultaneously. Under pentobarbital anesthesia, rats were subjected to unilateral nerve injury. Mechanical allodynia was tested for two weeks after nerve injury. After nerve injury, neuropathic pain behaviors developed progressively. The crossed-withdrawal reflex was observed at two weeks postoperatively. Contralateral enhancement of 2-DG uptake in the ventral horn of the spinal cord to electrical stimulation of the uninjured paw was observed. These results suggest that the facilitation of information processing from the uninjured side to the injured side may contribute to the crossed-withdrawal reflex by plastic changes in the spinal cord of nerve-injured rats.

94. The involvement of orexin (hypocretin) in the formalin-induced inflammatory pain response in adulthood following a neonatal bacterial immune challenge

Early life physiological stressors have been implicated in the onset of psychopathology in adulthood. In preclinical models, the neonatal bacterial immune challenge, lipopolysaccharide (LPS), has been shown to alter anxiety-like behaviour, neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a role for the lateral hypothalamic peptide orexin in stress, arousal and nociceptive processing. How a neonatal LPS exposure affects the reactivity of the orexin system to formalin-induced inflammatory pain in adulthood remains to be determined. Male Wistar rat pups (n = 12) were exposed to either LPS or saline (0.05 mg/kg, IP) on postnatal days (PND) 3 and 5. On PND 82–97, all rats were exposed to a subcutaneous hindpaw injection of 2.25% formalin (50 μL). 1.5 h following behavioural testing, animals were perfused and brains processed for Fos-protein and orexin immunohistochemistry. LPS-treated rats exhibited increased flinching but not licking responses in adulthood compared to saline controls (p

The German PASS-20 in patients with low back pain: new aspects of convergent, divergent, and criterion-related validity.

The PASS-20 (McCracken and Dhingra, Pain Res Manag 7:45-50, 2002) is a shortened version of the Pain Anxiety Symptoms Scale (PASS), a self-report measure of pain anxiety. The PASS-20 demonstrates good psychometric characteristics but has not yet been validated in a German population. The aims of the present study were to (1) examine the factor structure and psychometric characteristics of the German PASS-20; (2) investigate its construct validity with respect to depression, fear-avoidance, and endurance; and (3) determine its criterion-related validity with a special emphasis on pain, disability, and quality of life. A principal component analysis was performed on a sample (N = 195) of patients with acute, subacute, and chronic low back pain. Reliability was examined with Cronbach's α. Validity was assessed by correlating the PASS-20 to measures of depression, anxiety, disability, quality of life, and avoidance-endurance-related behavioral pain responses. The original four-factor structure proposed for the PASS-20 was replicated using the original subscale labels. The reliability of the total score and the subscales was satisfactory to excellent, and both convergent and divergent validity were moderate to high in the expected directions, showing positive correlations with anxiety, fear, depression, and fear-avoidance and negative correlations with endurance and quality of life. The PASS-20 showed unique predictive ability and advantages over the Tampa Scale of Kinesiophobia. The results for the German PASS-20 support the original factor structure and provide evidence of satisfactory psychometric characteristics and usefulness in patients with low back pain.

Functional and metabolic changes in the brain in neuropathic pain syndrome against the background of chronic epidural electrostimulation of the spinal cord.

Changes in functional and metabolic activities of the brain were evaluated by EEG and positron-emission/computer tomography with 18F-fluorodeoxyglucose in patients with neuropathic pain syndrome previous to and 3 months after implantation of a system for chronic epidural spinal cord stimulation. In most cases, the use of a nerve stimulator was followed by alleviation of neuropathic pain and partial normalization of functional and metabolic activities of brain structures responsible for pain perception, emotiogenic, behavioral, and autonomic responses.

SAT0554 Intra-Articular Injection of Mesenchymal Stem Cells Improves Pain Behaviour in A Model of OA Pain

BackgroundOsteoarthritis (OA) is a degenerative joint disease affecting around 8 million people in the UK. Pain is a prominent and often disabling feature of OA, the relationship between pain and...

Neuron-glial communication mediated by TNF-α and glial activation in dorsal root ganglia in visceral inflammatory hypersensitivity

Communication between neurons and glia in the dorsal root ganglia (DRG) and the central nervous system is critical for nociception. Both glial activation and proinflammatory cytokine induction underlie this communication. We investigated whether satellite glial cell (SGC) and tumor necrosis factor-α (TNF-α) activation in DRG participates in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat model of visceral hyperalgesia. In TNBS-treated rats, TNF-α expression increased in DRG and was colocalized to SGCs enveloping a given neuron. These SGCs were activated as visualized under electron microscopy: they had more elongated processes projecting into the connective tissue space and more gap junctions. When nerves attached to DRG (L6-S1) were stimulated with a series of electrical stimulations, TNF-α were released from DRG in TNBS-treated animals compared with controls. Using a current clamp, we noted that exogenous TNF-α (2.5 ng/ml) increased DRG neuron activity, and visceral pain behavioral responses were reversed by intrathecal administration of anti-TNF-α (10 μg·kg(-1)·day(-1)). Based on our findings, TNF-α and SGC activation in neuron-glial communication are critical in inflammatory visceral hyperalgesia.

A164: Development of Pediatric Item Banks to Measure Pain Behavior in the Patient Reported Outcomes Measurement Information System

Background/Purpose:The NIH Patient Reported Outcomes Measurement Information System (PROMIS) has created publicly available patient reported outcomes measures in several domains of physical, social and emotional health. Measurement of pediatric pain in PROMIS is currently limited to pain interference. Pain behaviors are observable actions orreactions that communicate pain including verbal, nonverbal and pain reducing behaviors. Numerous validated parent/provider‐rating scales of pain behavior in children exist but there are currently no validated self‐report measures of pain behavior in school‐age children and adolescents. Such measures could be useful in establishing targets for treatment and assessing outcomes. The aim of this study is to enhance PROMIS pediatric pain assessment by developing and testing pediatric pain behavior item banks for self‐ and proxy‐report.Methods:Candidate items were developed through a qualitative item review process, and were in the format, “In the past 7 days, when I was in pain …” Patients ages 8 to 17 years, or parents/guardians of children, with a chronic painful condition (fibromyalgia, juvenile idiopathic arthritis, sickle cell disease) were recruited through outpatient clinics at 3 centers. Child participants completed approximately 100 PROMIS items concerning their pain (including 47 candidate pain behavior items), physical function, fatigue, and psychosocial well/being. Proxies responded to sociodemographic and health history items and 51 new candidate proxy‐report pain behavior items were collected. A confirmatory factor analysis (CFA) was performed on the child and guardian pain behavior data, with model fit assessed by the comparative fit index (CFI) and root mean square error of approximation (RMSEA). Item response theory (IRT) analysis was performed on the pain behavior items based on the graded response model. Differential item functioning (DIF) was assessed by age group and disease group.Results:450 children (71% female, Mage 13.54), and 232 proxies participated. CFA indicated unidimensionality in the child (CFI = 0.962; RMSEA = 0.079) and proxy pain behavior responses (CFI = 0.970; RMSEA = 0.080). The responses for the child and proxy data had good IRT model fit and were free of local dependence. Slopes for the pediatric responses ranged from 1.81 (“rubbed body where hurt”) to 4.40 (“moved slower”), and thresholds ranged from −2.00 to 4.95. For the proxy data, slopes ranged from 1.51 (“think of something fun”) to 3.48 (“tried not to move”), and thresholds ranged from −3.02 to 2.43. Items performed well across disease groups and age. There was little DIF either by age group (8–12, 13–18) or by sample (child vs. proxy). Child and proxy scores were correlated at 0.70. Correlations between pain behavior and pain intensity were 0.60 in children and 0.65 in proxy sample.Conclusion:The PROMIS pediatric pain behavior item‐banks for self and proxy report are suitable for use in non‐adaptive format as short forms or in dynamic format as computerized adaptive tests in clinical research with the potential for adoption into clinical care.