Kristin L. Schreiber

Persistent pain in postmastectomy patients: comparison of psychophysical, medical, surgical, and psychosocial characteristics between patients with and without pain.

Summary Patients with and without persistent postmastectomy pain were tested. Psychosocial and psychophysical factors distinguished between groups more than demographic, surgical, and treatment‐related factors. Abstract Persistent postmastectomy pain (PPMP) is a major individual and public health problem. Increasingly, psychosocial factors such as anxiety and catastrophizing are being revealed as crucial contributors to individual differences in pain processing and outcomes. Furthermore, differences in patients’ responses to standardized quantitative sensory testing (QST) may aid in the discernment of who is at risk for acute and chronic pain after surgery. However, characterization of the variables that differentiate those with PPMP from those whose acute postoperative pain resolves is currently incomplete. The purpose of this study was to investigate important surgical, treatment‐related, demographic, psychophysical, and psychosocial factors associated with PPMP by comparing PPMP cases with PPMP‐free controls. Pain was assessed using the breast cancer pain questionnaire to determine the presence and extent of PPMP. Psychosocial and demographic information were gathered via phone interview, and women underwent a QST session. Consistent with most prior research, surgical and disease‐related variables did not differ significantly between cases and controls. Furthermore, treatment with radiation, chemotherapy, or hormone therapy was also not more common among those with PPMP. In contrast, women with PPMP did show elevated levels of distress‐related psychosocial factors such as anxiety, depression, catastrophizing, and somatization. Finally, QST in nonsurgical body areas revealed increased sensitivity to mechanical stimulation among PPMP cases, while thermal pain responses were not different between the groups. These findings suggest that an individual’s psychophysical and psychosocial profile may be more strongly related to PPMP than their surgical treatment.

Activation of spinal microglia in a murine model of peripheral inflammation-induced, long-lasting contralateral allodynia

Increased sensitivity contralateral to an injury has been described in humans and in various models of neuropathic pain in rats. The mechanism underlying contralateral hypersensitivity is as yet unclear, although previous studies have implicated involvement of both spinal neurons and glia. We describe the development of a temporally delayed, robust and long-lasting contralateral allodynia in mice after hindpaw injection with 4% carrageenan. Both ipsilateral and contralateral allodynia could be inhibited temporarily by intrathecally administered morphine, clonidine, or neostigmine. The delayed development of contralateral allodynia correlated with an increase in OX-42, but not GFAP immunoreactivity in the contralateral dorsal horn. Furthermore, intrathecal treatment with minocycline inhibited the development of contralateral allodynia, suggesting that microglial activation plays a key role in contralateralization, and may be a potential target for clinical intervention after injury or inflammation has occurred, to eliminate the subsequent development of extraterritorial pain.

Alteration in Pain Modulation in Women With Persistent Pain After Lumpectomy: Influence of Catastrophizing

CONTEXT Persistent pain is common after surgical treatment of breast cancer, but fairly little is known about the changes in sensory processing that accompany such pain syndromes. OBJECTIVES This study used quantitative sensory testing to compare psychophysical responses to standardized noxious stimulation in two groups of women who had previously undergone breast cancer surgery: women with (n=37) and without (n=34) persistent postoperative pain. METHODS Participants underwent a single testing session in which responses to a variety of noxious stimuli were assessed. RESULTS Findings suggested that women with chronic pain after breast cancer surgery display enhanced temporal summation of mechanical pain, deficits in endogenous pain inhibition, and more intense painful aftersensations compared with those without long-term pain. Some of these group differences were mediated by higher levels of pain catastrophizing in the group of women with persistent pain. CONCLUSION These findings suggest that persistent postoperative pain is associated with alterations in central nervous system pain-modulatory processes. Future treatment studies might benefit from targeting these pain-modulatory systems, and additional studies using functional neuroimaging methods might provide further valuable information about the pathophysiology of long-term postsurgical pain in women treated for breast cancer.

Predicting, preventing and managing persistent pain after breast cancer surgery: the importance of psychosocial factors

Persistent pain after breast cancer surgery (PPBCS) is increasingly recognized as a potential problem facing a sizeable subset of the millions of women who undergo surgery as part of their treatment of breast cancer. Importantly, an increasing number of studies suggest that individual variation in psychosocial factors such as catastrophizing, anxiety, depression, somatization and sleep quality play an important role in shaping an individuals risk of developing PPBCS. This review presents evidence for the importance of these factors and puts them within the context of other surgical, medical, psychophysical and demographic factors, which may also influence PPBCS risk, as well as discusses potential perioperative therapies to prevent PPBCS.

Adrenocorticotrophic hormone modulates Escherichia coli O157: H7 adherence to porcine colonic mucosa

Exposure to stress is associated with susceptibility to disease and one stress mediator, norepinephrine, has been reported to enhance the adherence of enterohemorrhagic Escherichia coli O157:H7 (EHEC) to the colonic mucosa. We tested the hypothesis that adrenocorticotropic hormone (ACTH) and other stress-related hormones may act in a similar fashion. Explants of distal colonic mucosa from young pigs were mounted in Ussing chambers and their luminal aspect was exposed to EHEC strain 700728 for 30–90 min. When added to the contraluminal, but not luminal bathing medium, ACTH increased EHEC adherence within 90 min in a concentration-dependent manner (EC50 = 1.2 nM), but did not alter tissue electrical conductance. ACTH had no effect on the adherence of a pig-adapted non-O157 E. coli strain. The effect of 0.1 μM ACTH on luminal EHEC adherence was prevented in tissues pretreated contraluminally with the type 2 melanocortin receptor antagonist ACTH7–38, the neuronal conduction blocker saxitoxin, or the muscarinic cholinergic antagonist atropine. Moreover, ACTH7–38 decreased EHEC adherence in the absence of ACTH. These results suggest that ACTH acts via melanocortin receptors located on enteric nerves to enhance mucosal adherence of EHEC.

Distraction analgesia in chronic pain patients: the impact of catastrophizing.

Background:Diverting attention away from noxious stimulation (i.e., distraction) is a common pain-coping strategy. Its effects are variable across individuals, however, and the authors hypothesized that chronic pain patients who reported higher levels of pain catastrophizing would derive less pain-reducing benefit from distraction. Methods:Chronic pain patients (n = 149) underwent psychometric and quantitative sensory testing, including assessment of the temporal summation of pain in the presence and absence of a distracting motor task. Results:A simple distraction task decreased temporal summation of pain overall, but, surprisingly, a greater distraction analgesia was observed in high catastrophizers. This enhanced distraction analgesia in high catastrophizers was not altered when controlling for current pain scores, depression, anxiety, or opioid use (analysis of covariance [ANCOVA]: F = 8.7, P < 0.005). Interestingly, the magnitude of distraction analgesia was inversely correlated with conditioned pain modulation (Pearson R = −0.23, P = 0.005). Conclusion:Distraction produced greater analgesia among chronic pain patients with higher catastrophizing, suggesting that catastrophizing’s pain-amplifying effects may be due in part to greater attention to pain, and these patients may benefit from distraction-based pain management approaches. Furthermore, these data suggest that distraction analgesia and conditioned pain modulation may involve separate underlying mechanisms.

Epidural Versus Paravertebral Nerve Block for Postoperative Analgesia in Patients Undergoing Open Liver Resection: A Randomized Clinical Trial.

Background and Objectives Although many studies have found no difference between thoracic epidural block and unilateral thoracic paravertebral block after thoracotomy, no previous studies have compared epidural block with bilateral thoracic paravertebral block (bTPVB) in patients undergoing open liver resection. We aimed to investigate whether there was a significant analgesic advantage of thoracic epidural over bTPVB after liver resection. Methods This randomized, prospective, open-label study included adult patients undergoing elective open liver resection. Patients were randomized to receive either thoracic epidural block or bTPVB, through which ropivacaine (0.2%) was infused for 3 days. The primary outcome was pain Verbal Rating Scale (VRS) score (0–10) at rest and with postoperative incentive spirometry. Secondary outcomes included VRS at rest, inspired volumes during incentive spirometry, patient-controlled analgesia hydromorphone utilization, measures of hemodynamic stability, and postoperative bowel function. Results Eighty patients completed the study and received thoracic epidural block (n = 41) or bTPVBs (n = 39). No catheter-related complications were noted. The primary outcome, pain (VRS) with incentive spirometry, was significantly lower in the epidural group (epidural vs bTPVB, mean [SD]) (4.5 [2.7] vs 5.4 [2.7] at 24 hours postoperatively, and 3.2 [2.1] vs 4.6 [2.4] at 48 hours postoperatively). Maximal inspired volumes at 24 hours postoperatively (917 [379] vs 1042 [468] mL) and cumulative utilization of patient-controlled analgesia hydromorphone during the first 48 hours postoperatively (10.7 [7.9] vs 13.6 [8.5] mg) were not significantly different between groups. Decrease in mean arterial pressure from baseline at 24 hours postoperatively was greater for the epidural group (−12.6 [15.8] vs −3.8 [16.2]; P = 0.016). Conclusions This study suggests that there is a modest analgesic advantage of thoracic epidural over bTPVBs for patients after open liver resection.

Music as an Adjunct to Opioid-Based Analgesia

Epidemic increases in opioid use in the USA and globally highlight the need for effective adjunctive therapies to opioid-based analgesia. Given the shortcomings of behavioral adjuncts to opioid-based pain treatment, an urgent need exists for pain-related behavioral interventions that resonate with broad patient populations, can be delivered confidentially in any environment, and can incorporate new content automatically. Understanding the potential for automated behavioral therapies like music therapy in modulating the experience of pain may unlock methods to transition patients to lower doses of pharmacologic therapy or provide alternatives to opioids during acute exacerbations of pain. This manuscript describes the neurologic mechanism of action, theoretical basis, and potential applications of personalized music as a smartphone-based mHealth intervention for acute and chronic pain management.

Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills

BACKGROUND: Opioid analgesics are commonly prescribed on an as-needed (PRN) basis for acute painful conditions. Uncertainty of how patients actually take PRN opioids, coupled with a desire to completely cover pain, leads to variable and overly generous opioid prescribing practices, resulting in a surplus of opioids. This opioid surplus becomes a source for diversion and nonmedical opioid use. Understanding patterns of actual opioid ingestion after acute painful conditions can help clinicians counsel patients on safe opioid use, and allow timely recognition and intervention when escalating opioid self-dosing occurs, to prevent tolerance and addiction. METHODS: We used a novel oxycodone digital pill system (ingestible biosensor within a standard gelatin capsule combined with 5-mg oxycodone) that when ingested, is activated by the chloride ion gradient in the stomach thereby emitting a radiofrequency signal captured by a wearable reader. The reader relays ingestion data to a cloud-based server that displays ingestion events to the study team. We deployed the oxycodone digital pill among opioid-naive individuals discharged from the emergency department with acute fracture pain. Participants were trained on digital pill operation and discharged with twenty-one 5-mg oxycodone digital pills. They were instructed to take digital pills PRN for pain on discharge. We conducted a brief interview 7 days after study enrollment, at which point participants returned the digital pill system. We identified oxycodone ingestion events in real time by data from the digital pill system and performed pill counts at the return visit to validate digital pill reporting of medication ingestion. RESULTS: In this study, 26 individuals were approached; 16 enrolled with 15 completing the study. Participants ingested a median of 6 (3–9.5) oxycodone digital pills over the course of 7 days, with 82% of the oxycodone dose ingested in the first 3 days. In individuals who required operative repair, 86% (N = 6) continued to ingest opioids at 1 week. There was substantial variability in ingestion patterns between individuals. CONCLUSIONS: The utilization patterns of individuals with acute fracture pain could be captured using a digital pill system and revealed a median opioid ingestion of 45-mg morphine equivalents for acute pain over 7 days. Seven participants ceased using opioids within 4 days after discharge from the emergency department, although operative repair was associated with longer use. This digital pill system was able to measure changes in and patterns of opioid self-dosing, which varied between patients.

Prediction of Pain and Opioid Utilization in the Perioperative Period in Patients Undergoing Primary Knee Arthroplasty: Psychophysical and Psychosocial Factors

Objective To identify factors associated with pain severity and opioid consumption in the early perioperative period. Design Prospective observational cohort study. Setting Tertiary academic medical center. Subjects Patients with osteoarthritis older than age 45 years undergoing primary total knee replacement at Brigham and Womens Hospital. A total of 126 patients enrolled. Methods Preoperatively, pain questionnaires and quantitative sensory testing were performed on patients to develop a psychosocial and psychophysical profile. Postoperatively, pain scores and opioid consumption were measured as primary end points. Univariate and multiple linear regression analyses were performed to determine the predictive value of these characteristics on perioperative pain scores and opioid consumption. Results Regression analysis revealed several predictors of acute postoperative pain scores including temporal summation of pain (TSP; P = 0.001), body mass index (BMI; P = 0.044), number of previous knee surgeries (P = 0.006), and female gender (P = 0.023). Similarly, predictors of opioid utilization included TSP (P = 0.011), BMI (P = 0.02), age (P = <0.001), and tourniquet time (P = 0.003). Conclusions The only significant, unique predictors of both pain and opioid consumption were TSP, an index of central pain facilitatory processes, and BMI. Interestingly, psychosocial factors, such as catastrophizing and somatization, although correlated with postoperative pain scores and opioid consumption, generally did not independently explain substantial variance in these measures. This study suggests that BMI and quantitative sensory testing, specifically the temporal summation of pain, may provide value in the preoperative assessment of patients undergoing total knee arthroplasty and other surgeries via predicting their level of risk for adverse pain outcomes.