Resolution Of Acute Pain Research Articles

Omics approaches to discover pathophysiological pathways contributing to human pain.

Omics approaches to discover pathophysiological pathways contributing to human pain.

IGF1-driven induction of GPCR kinase 2 in the primary afferent neuron promotes resolution of acute hyperalgesia

Dynamic regulation of G-protein-coupled receptor (GPCR) kinase 2 (GRK2) expression restores cellular function by protecting from overstimulation via GPCR and non-GPCR signaling. In the primary afferent neurons, GRK2 negatively regulates nociceptive tone. The present study tested the hypothesis that induction of GRK2 in the primary afferent neurons contributes to the resolution of acute pain after tissue injury.GRK2 expression in the dorsal root ganglion (DRG) was analyzed at 1 and 7 days after the incision. Intraperitoneal administration of a GRK2 inhibitor was performed 7 days post-incision in male Sprague-Dawley rats who underwent plantar incisions to analyze the pain-related behavioral effect of the GRK2 inhibitor. Separately, GRK2 expression was analyzed after injecting insulin-like growth factor 1 (IGF1) into the rat hind paw. In addition, an IGF1 receptor (IGF1R) inhibitor was administered in the plantar incision rats to determine its effect on the incision-induced hyperalgesia and GRK2 expression.Plantar incision induced an increase in GRK2 in the DRG at 7 days, but not at 1 day post-incision. Acute hyperalgesia after the plantar incision disappeared by 7 days post-incision. Intraperitoneal injection of the GRK2 inhibitor at this time reinstated mechanical hyperalgesia, although the GRK2 inhibitor did not produce hyperalgesia in naive rats. After the incision, IGF1 expression increased in the paw, but not in the DRG. Intraplantar injection of IGF1 increased GRK2 expression in the ipsilateral DRG. IGF1R inhibitor administration prevented both the induction of GRK2 and resolution of hyperalgesia after the plantar incision.These findings demonstrate that induction of GRK2 expression driven by tissue IGF1 has potent analgesic effects and produces resolution of hyperalgesia after tissue injury. Dysregulation of IGF1-GRK2 signaling could potentially lead to failure of the spontaneous resolution of acute pain and, hence, development of chronic pain after surgery.

P030: Acute pain resolution after an emergency department visit: a 14-day trajectory analysis

Introduction: The objective of the study was to evaluate the acute pain intensity evolution in ED discharged patients using Group-based trajectory modeling (GBTM). This method identified patient groups with similar profiles of change over time without assuming the existence of a particular pattern or number of groups. Methods: This was a prospective cohort study of ED patients aged ≥18 years with an acute pain condition (≤ 2 weeks) and discharged with an opioid prescription. Patients completed a 14-day diary assessing daily pain intensity level (0-10 numeric rating scale) and pain medication use. Results: Among the 372 included patients, six distinct post-ED pain intensity trajectories were identified: two started with severe levels of pain, one remained with severe pain intensity (12.6% of the sample) and the other ended with moderate pain intensity level (26.3%). Two other trajectories had severe initial pain, one decreased to mild pain (21.7%) and the other to no-pain (13.8%). Another trajectory had moderate initial pain which decreased to a mild level (15.9%) and the last one started with mild pain intensity and had no pain at the end of the 14-day (9.7%). The pain trajectory patterns were significantly associated with age, type of painful conditions, pain intensity at ED discharge, and with opioid consumption. Conclusion: Acute pain resolution following an ED visit seems to progress through six different trajectory patterns that are more informative than simple linear models and could be useful to adapt acute pain management in future research.

Acute Pain Resolution After an Emergency Department Visit: A 14-Day Trajectory Analysis

The objective of the study is to evaluate the acute pain intensity evolution in emergency department (ED) discharged patients, using group-based trajectory modeling. This method identifies patient groups with similar profiles of change over time without assuming the existence of a particular pattern or number of groups. This was a prospective cohort study of ED patients aged 18 years or older, with an acute pain condition (≤2 weeks), and discharged with an opioid prescription. Patients completed a 14-day diary assessing daily pain intensity level (numeric rating scale of 0 to 10) and pain medication use. Among the 372 included patients, 6 distinct post-ED pain intensity trajectories were identified. Two started with severe levels of pain; one remained with severe pain intensity (12.6% of the sample) and the other ended with a moderate pain intensity level (26.3%). Two other trajectories had severe initial pain; one decreased to mild pain (21.7%) and the other to no pain (13.8%). Another trajectory had moderate initial pain that decreased to a mild level (15.9%) and the last one started with mild pain intensity and had no pain at the end of the 14-day period (9.7%). The pain trajectory patterns were significantly associated with age, type of painful conditions, pain intensity at ED discharge, and opioid consumption. Acute pain resolution after an ED visit seems to progress through 6 different trajectory patterns that are more informative than simple linear models and could be useful to adapt acute pain management in future research.

Distinct Analgesic Actions of DHA and DHA-Derived Specialized Pro-Resolving Mediators on Post-operative Pain After Bone Fracture in Mice.

Mechanisms of pain resolution are largely unclear. Increasing evidence suggests that specialized pro-resolving mediators (SPMs), derived from fish oil docosahexaenoic acid (DHA), promote the resolution of acute inflammation and potently inhibit inflammatory and neuropathic pain. In this study, we examined the analgesic impact of DHA and DHA-derived SPMs in a mouse model of post-operative pain induced by tibial bone fracture (fPOP). Intravenous perioperative treatment with DHA (500 μg), resolvin D1 (RvD1, 500 ng) and maresin 1 (MaR1, 500 ng), 10 min and 24 h after the surgery, delayed the development of fPOP (mechanical allodynia and cold allodynia). In contrast, post-operative intrathecal (IT) administration of DHA (500 μg) 2 weeks after the surgery had no effects on established mechanical and cold allodynia. However, by direct comparison, IT post-operative treatment (500 ng) with neuroprotectin D1 (NPD1), MaR1, and D-resolvins, RvD1 and RvD5, but not RvD3 and RvD4, effectively reduced mechanical and cold allodynia. ELISA analysis showed that perioperative DHA treatment increased RvD1 levels in serum and spinal cord samples after bone fracture. Interestingly, sham surgery resulted in transient allodynia and increased RvD1 levels, suggesting a correlation of enhanced SPM levels with acute pain resolution after sham surgery. Our findings suggest that (1) perioperative treatment with DHA is effective in preventing and delaying the development of fPOP and (2) post-treatment with some SPMs can attenuate established fPOP. Our data also indicate that orthopedic surgery impairs SPM production. Thus, DHA and DHA-derived SPMs should be differentially supplemented for treating fPOP and improving recovery.

Safety and Efficacy of Different Systemic Treatment Modalities for Acute Pain of Herpes Zoster: A Pilot Study.

Background:Herpes zoster is a viral infection of skin caused by Varicella Zoster virus. The most important symptom for which the patient seeks medical advice is pain, which is perceived before the development of rash and lasts even after its resolution. The pain during the first 30 days after onset of herpes zoster is known as acute herpetic neuralgia. The aim of this study was to compare the efficacy and side-effects of different systemic treatment modalities for acute herpes zoster neuralgia.Materials and Methods:This was a randomized, single-blind, parallel control study. Forty-five patients of herpes zoster within 72 hours of onset were enrolled after considering various inclusion and exclusion criteria over a duration of 1 year. Pain severity was assessed after sequential distribution and allotment of patients in three groups using verbal rating scale (VRS). Patients in Group A (control group), were treated with Tab.valacyclovir (1 g tds × 7 days), Group B–Tab.valacyclovir (1 g tds × 7 days) + Cap. Pregabalin (75 mg bd × 1 month), and Group C –Tab.valacyclovir (1 g tds × 7 days) +Cap. Pregabalin (75 mg bd × 1 month) + Tab.methylprednisolone (0.64 mg/kg body weight in two divided doses × 7 days). Patients were followed up at 1, 4, 6 weeks. Complete resolution of acute pain and side-effects were noted.Results:At the end of 4 weeks, reduction in acute pain was statistically significant (P < 0.05) in all the three groups individually compared to the baseline value. At the end of 6 weeks, percentage of patients with persistence of pain was more in Group A and B compared to Group C, which was statistically significant (P = 0.0001). In group A, postherpetic neuralgia was observed in more patients compared to group B and C. No significant side-effects were observed in any group except vomiting, somnolence, and dizziness.Limitations:Sample size of this study was limited. Further studies with large sample size are required to further validate the findings of the present study.Conclusions:Combination therapy with valacyclovir, methylprednisolone, and pregabalin has better efficacy compared to valacyclovir and pregabalin and valacyclovir alone in the management of acute herpes zoster neuralgia. No significant side-effects were observed

Percentage of pain intensity difference on an 11‐point numerical rating scale underestimates acute pain resolution

A 50% reduction in pain intensity difference (50%PID) between baseline and follow-up evaluation is commonly accepted as adequate pain relief in emergency departments (EDs). However, 50%PID seems to be problematic with the 11-point numerical rating scale (NRS) since even baseline values are more divisible by 2 (50% reduction) than odd baseline values. This study evaluated the impact of this bias and integrated time between baseline and follow-up measurements, hypothesizing that the slope of relative pain intensity difference (SRPID) is a more accurate gauge of pain relief that can decrease bias and incorporate the time component of pain relief. A post-hoc analysis of real-time data on an adult population from an urban ED identified 3199 consecutive patients who received an analgesic, had baseline NRS > 3 and a follow-up NRS within 2 h. Primary outcome was the percentage of patients with pain relieved from the 50%PID and the 50%SRPID criteria. Results showed that with 50%PID, even pain intensity levels on baseline NRS comprised a higher percentage of patients [60.7%; 95% confidence interval (CI): 58.8-63.0] with pain relief compared to odd pain intensity levels (51.7%; 95% CI: 48.8-54.6; p < 0.001), underestimating pain-relieved patients by 9% [95% CI: 0.05-0.13; effect size (ES) = 0.09]. The percentage of pain-relieved subjects with the 50%SRPID criteria was not affected by baseline NRS values (59.7% for whole sample; 95% CI: 58.0-61.4; ES = 0.02). The 50%PID method with an 11-point NRS for assessing adequate pain relief is significantly biased for specific baseline pain intensity level. In the particular context of ED acute pain, the SRPID seems less biased.

Distinguishing between pain intensity and pain resolution: Using acute post‐surgical pain trajectories to predict chronic post‐surgical pain

High intensity of acute post-surgical pain is one of the strongest predictors for chronic post-surgical pain (CPSP). We investigated the predictive power of acute post-surgical pain trajectories and the interplay of pain trajectories and diverse psychosocial risk factors in the development of CPSP. Data from 199 patients were examined using latent growth curve analysis by means of structural equation modelling. This analytical approach was used to explicitly test the mediating role of acute pain trajectories within the association between preoperative psychosocial vulnerability factors and CPSP. Both initial pain intensity and pain resolution during the first five post-operative days independently contributed to the prediction of CPSP 6 months after surgery. In terms of vulnerability, anxiety and depression had clear but opposing effects on post-operative pain trajectories. Whereas depressive patients exhibited impaired pain resolution, patients with high anxiety showed better rates of pain resolution after surgery. Both effects on acute pain resolution extended to chronic pain 6 months after surgery. In this study, we demonstrated that going beyond conventional one-time measurements of acute pain by modelling pain trajectories may substantially enhance research on pain chronification in two ways: First, pain trajectories bear great potential to improve the prediction of CPSP. Second, they represent a meaningful link between psychosocial vulnerability and CPSP because they can be used to uncover mechanisms by which psychosocial vulnerability unfolds. The reported findings suggest that the incidence of CPSP may be reduced by optimizing post-operative pain monitoring.

Reversal of Peripheral Nerve Injury-induced Hypersensitivity in the Postpartum Period

Physical injury, including surgery, can result in chronic pain; yet chronic pain following childbirth, including cesarean delivery in women, is rare. The mechanisms involved in this protection by pregnancy or delivery have not been explored. We examined the effect of pregnancy and delivery on hypersensitivity to mechanical stimuli of the rat hindpaw induced by peripheral nerve injury (spinal nerve ligation) and after intrathecal oxytocin, atosiban, and naloxone. Additionally, oxytocin concentration in lumbar spinal cerebrospinal fluid was determined. Spinal nerve ligation performed at mid-pregnancy resulted in similar hypersensitivity to nonpregnant controls, but hypersensitivity partially resolved beginning after delivery. Removal of pups after delivery prevented this partial resolution. Cerebrospinal fluid concentrations of oxytocin were greater in normal postpartum rats prior to weaning. To examine the effect of injury at the time of delivery rather than during pregnancy, spinal nerve ligation was performed within 24 h of delivery. This resulted in acute hypersensitivity that partially resolved over the next 2-3 weeks. Weaning of pups resulted only in a temporary return of hypersensitivity. Intrathecal oxytocin effectively reversed the hypersensitivity following separation of the pups. Postpartum resolution of hypersensitivity was transiently abolished by intrathecal injection of the oxytocin receptor antagonist, atosiban. These results suggest that the postpartum period rather than pregnancy protects against chronic hypersensitivity from peripheral nerve injury and that this protection may reflect sustained oxytocin signaling in the central nervous system during this period.

Resolution of Acute Pain Following Discharge From the Emergency Department: The Acute Pain Trajectory

We demonstrate and evaluate a method for modeling acute pain resolution in individual patients over 6 days following an emergency department visit for an acutely painful condition. Five hundred and thirteen patients presenting with acutely painful conditions provided 11-point numerical ratings of pain intensity at discharge from an emergency department and daily thereafter for a total of 6 days. Latent growth curve modeling with a linear fit yielded measures of initial pain intensity (intercept) and rate of pain resolution (slope) for each individual patient. The linear fits provided good approximations of individual pain trajectories. The average patient had intercept of 6.57 with a slope of −.61. On Day 4, 54.6% of patients reported a pain level equal to or greater than 4. Classification of individual patients by slope revealed that 79% of the sample had the expected negative slope for acute pain resolution while 21% had flat or positive slopes, indicating lack of pain resolution or worsening of pain over time following discharge. The standard errors of measurement for the acute pain trajectories were markedly smaller than those for conventional pain ratings, indicating that the trajectory approach to pain measurement improves measurement precision. PerspectiveThe acute pain trajectory provides more information than conventional pain measurement and increases measurement precision. It provides a means of determining the efficacy of acute pain management in the emergency department. The rate of pain resolution is a potentially valuable outcome measure for controlled clinical trials.

The progression from acute to chronic pain

The persistence of pain after surgical procedure or trauma has become a major focus of interest and its prevention now represents a challenge as an indicator of quality of healthcare. The only way to develop effective strategies to prevent the development of chronic pain is to better understand the mechanisms involved in the progression from acute to chronic pain, with the aim to target high-risk patients and to adapt perioperative management. Several important risk factors involved in chronic pain development after tissue injury have been identified, underlining how much the phenomenon is complex and multifaceted. Recent studies have highlighted some important points on which to focus, mainly during the acute and subacute postinjury periods. These studies promote a more dynamic approach related to a better evaluation of acute pain resolution using individualized pain trajectories, the assessment of endogenous pain-modulatory processes and individual's psychological flexibility when facing physical threat and pain. A dynamic view of both physiological and psychological response of an individual after injury (trauma, surgery) should improve our ability to target predisposed patients who might develop persistent pain. We should then be more able to provide those patients with the most appropriate preventive management.

Psychological changes and the resolution of acute neck pain after a motor vehicle accident

This study examines the changes in self-perception during resolution of an acutely painful neck injury sustained in a motor vehicle accident. We tested predictions from self-discrepancy theory and a model of self-pain enmeshment. Measures of discrepancy between the current (actual) self and both the ideal and feared-for self were predicted to remain stable over a 21-day recovery period whereas a measure of enmeshment was predicted to decrease as pain resolved. We also examined the relationship between daily ratings of achievement in several domains and participants perceived ideal performance. Sixty patients with possible acute neck injury recruited within 1 month after a motor vehicle accident gave consent and data were obtained from 42 participants. Standard questionnaire measures of pain, disability, fear of movement, pain catastrophizing and self-discrepancies, self-pain enmeshment and data from diaries (measures of pain, mood, self-discrepancies, pain catastrophizing and fear of movement) were obtained. In general the relationships between the measures of self-discrepancy and enmeshment and mood were in accord with both theoretical predictions and previous observations. Resolution of pain was associated with a reduction in enmeshment but not to change in self-discrepancy. Multilevel analyses of the diary data showed that concordance between actual and ideal performance increased over the 21 days of data collection. These data provide preliminary support for aspects of self-discrepancy theory and the self-pain enmeshment model.

Meeting patient expectations in migraine treatment: what are the key endpoints?

Clinical outcomes of migraine treatment are generally based on two major endpoints: acute pain resolution and effects on quality of life (QOL). Resolution of acute pain can be evaluated in a number of ways, each increasingly challenging to achieve; pain relief, pain freedom at 2 h, sustained pain-freedom, and SPF plus no adverse events (SNAE, the most challenging). QOL questionnaires help assess the burden of migraine and identify optimal treatments. Pain resolution and improved QOL form the basis of the ultimate target—meeting patient expectations, to achieve patient satisfaction. To achieve this, it is crucial to choose appropriate endpoints that reflect realistic treatment goals for individual patients. Moreover, SNAE can help discriminate between triptans, with almotriptan having the highest SNAE score. Kaplan–Meier plots are also relevant when evaluating migraine treatments. The use of symptomatic medication may lead to the paradoxical development of medication-overuse headache. In general practice, patients should use simple tools for pain measurement (e.g. headache diary) and a QOL questionnaire. A composite endpoint of pain resolution and QOL restoration would constitute a step forward in migraine management.

Adenine Arabinoside for Therapy of Herpes Zoster in Immunosuppressed Patients: Preliminary Results of a Collaborative Study

Eighty-seven immunosuppressed patients (53 with localized and 34 with disseminated herpes zoster) from 10 institutions were enrolled in a controlled therapeutic trial of adenine arabinoside. A crossover design was employed; thus, 47 patients received drug for five days and then received placebo, and 40 were given the two substances in the opposite order. Resolution of acute pain and the cutaneous lesions were graded during a 10-day observation period. During the initial five-day period, treated patients showed a statistically significant resolution of pain and cutaneous lesions. Surprisingly, in many untreated patients, natural resolution occurred during this period so that crossover data could not be adequately assessed. Effects on visceral disease also could not be judged, because such disease was uncommon. Ratings of late complications such as postherpetic neuralgia were confused by the crossover design. Toxicity posed no problem. The data further emphasized the potential usefulness of adenine arabinoside as an antiviral chemotherapeutic agent, but also clearly indicated the need for a double-blind study to define this usefulness and to determine how it can most practically be used, if the risk-benefit factor remains favorable.