Palmar Telangiectasias: A Cutaneous Sign for Smoking.

BACKGROUND: Telangiectasias are permanent dilations of blood capillaries which appear in a variety of medical conditions. Cutaneous palmar telangiectasias have been postulated to be associated with smoking. OBJECTIVE: To determine whether a significant correlation exists between palmar telangiectasias and smoking habits. PATIENTS AND METHODS: A total of 124 volunteers participated in this observational study by allowing physical evaluation of their palms and by completing a questionnaire. RESULTS: Palmar telangiectasias were found to be associated with current or past smoking. Neither age nor gender was found to be a co-contributor. DISCUSSION: Palmar telangiectasias were found to constitute highly specific and sensitive markers for prolonged smoking.

Activation of Peripheral µ-opioid Receptors by Dermorphin [D-Arg2, Lys4] (1-4) Amide Leads to Modality-preferred Inhibition of Neuropathic Pain.

BACKGROUND: Opioids have long been regarded as the most effective drugs for the treatment of severe acute and chronic pain. Unfortunately, their therapeutic efficacy and clinical utility have been limited because of central and peripheral side effects. METHODS: To determine the therapeutic value of peripheral µ-opioid receptors as a target for neuropathic pain treatment, the authors examined the effects of dermorphin [D-Arg2, Lys4] (1-4) amide (DALDA), a hydrophilic, peripherally acting µ-opioid receptor agonist, in male and female rats with spinal nerve ligation-induced neuropathic pain. The authors also utilized behavioral, pharmacologic, electrophysiologic, and molecular biologic tools to characterize DALDA's possible mechanisms of action in male rats. RESULTS: DALDA, administered subcutaneously, had 70 times greater efficacy for inhibiting thermal (n = 8 to 11/group) than mechanical hypersensitivity (n = 6 to 8/group) in male rats. The pain inhibitory effects of DALDA on mechanical and heat hypersensitivity were abolished in animals pretreated with systemic methylnaltrexone (n = 7 to 9/group), a peripheral µ-opioid receptor antagonist. In the spinal wide-dynamic range neurons, systemic DALDA inhibited C-fiber-mediated, but not A-fiber-mediated, response in neuropathic male rats (n = 13). In primary sensory neurons, DALDA inhibited the capsaicin-induced [Ca2+] increase more than the ß-alanine-induced [Ca] increase (n = 300); capsaicin and ß-alanine activate subpopulations of neurons involved in the signaling of heat and mechanical pain, respectively. DALDA-treated rats (n = 5 to 8/group) did not exhibit motor deficits and locomotor impairment suggesting that it does not induce central side effects. CONCLUSIONS: These findings suggest that DALDA may represent a potential alternative to current opioid therapy for the treatment of neuropathic pain and is likely to be associated with minimal adverse effects.

Conventional and kilohertz-frequency spinal cord stimulation produces intensity- and frequency-dependent inhibition of mechanical hypersensitivity in a rat model of neuropathic pain.

BACKGROUND: Spinal cord stimulation (SCS) is a useful neuromodulatory technique for treatment of certain neuropathic pain conditions. However, the optimal stimulation parameters remain unclear. METHODS: In rats after L5 spinal nerve ligation, the authors compared the inhibitory effects on mechanical hypersensitivity from bipolar SCS of different intensities (20, 40, and 80% motor threshold) and frequencies (50, 1 kHz, and 10 kHz). The authors then compared the effects of 1 and 50 Hz dorsal column stimulation at high- and low-stimulus intensities on conduction properties of afferent Aα/ß-fibers and spinal wide-dynamic-range neuronal excitability. RESULTS: Three consecutive daily SCS at different frequencies progressively inhibited mechanical hypersensitivity in an intensity-dependent manner. At 80% motor threshold, the ipsilateral paw withdrawal threshold (% preinjury) increased significantly from pre-SCS measures, beginning with the first day of SCS at the frequencies of 1 kHz (50.2 ± 5.7% from 23.9 ± 2.6%, n = 19, mean ± SEM) and 10 kHz (50.8 ± 4.4% from 27.9 ± 2.3%, n = 17), whereas it was significantly increased beginning on the second day in the 50 Hz group (38.9 ± 4.6% from 23.8 ± 2.1%, n = 17). At high intensity, both 1 and 50 Hz dorsal column stimulation reduced Aα/ß-compound action potential size recorded at the sciatic nerve, but only 1 kHz stimulation was partially effective at the lower intensity. The number of actions potentials in C-fiber component of wide-dynamic-range neuronal response to windup-inducing stimulation was significantly decreased after 50 Hz (147.4 ± 23.6 from 228.1 ± 39.0, n = 13), but not 1 kHz (n = 15), dorsal column stimulation. CONCLUSIONS: Kilohertz SCS attenuated mechanical hypersensitivity in a time course and amplitude that differed from conventional 50 Hz SCS, and may involve different peripheral and spinal segmental mechanisms.

A multidisciplinary transitional pain service to improve pain outcomes following trauma surgery: a preliminary report.

OBJECTIVES: Trauma (i.e., musculoskeletal injury from a blunt or penetrating force) can change the trajectory of a person's life. Patients often experience chronic pain, reduced quality of life, long-term opioid therapy, and psychiatric comorbidities after trauma surgery. This case report presents clinical outcomes of four patients who received postsurgical pain care in a transitional pain service (TPS) that provides long-term coordinated multimodal pain care, opioid tapering plans, and psychiatric care. METHODS: The Personalized Pain Program (PPP) measures prescription opioid use and patient-reported outcomes: pain severity and pain interference (Brief Pain Inventory), pain catastrophizing (Pain Catastrophizing Scale), insomnia severity (Insomnia Severity Index), physical and mental health functioning (SF-12 pre-COVID-19; SF-36 during COVID-19 pandemic) at initial and subsequent clinic visits. RESULTS: All four patients reduced their postsurgical opioid use with concurrent reductions in pain and improved functioning while receiving postoperative care in the PPP (average length of treatment: 2.8 years). Psychiatric co-treatment addressed the onset or exacerbation of mental health comorbidities following trauma. CONCLUSIONS: Long-term multidisciplinary pain care may improve post-trauma recovery and reduce risks of long-term opioid therapy and disability. Prospective studies are needed to evaluate the effectiveness of TPSs for patients undergoing trauma surgery.

The use of telemedicine for perioperative pain management during the COVID-19 pandemic.

INTRODUCTION: Using a human factors engineering approach, the Johns Hopkins Personalized Pain Program adopted telemedicine for perioperative pain management in response to the COVID-19 pandemic. This study examines the impact of telemedicine adoption on the quality and outcomes of perioperative pain management. METHODS: A mixed-methods study with a convergent parallel design was conducted. From June 2017 to December 2021, 902 patients participated in the Personalized Pain Program. Quantitative data on daily opioid consumption, pain severity and interference, physical and mental health status, and patient satisfaction and engagement were continuously collected with all patients using chart review and patient surveys. Beginning 23 March 2020, the Personalized Pain Program transitioned to telemedicine. A pre-post quasi-experimental design was used to examine the impact of telemedicine. In addition, qualitative interviews were conducted with 3 clinicians and 17 patients to explore their experience with telemedicine visits. RESULTS: The monthly number of new patients seen in the Personalized Pain Program did not significantly change before and after telemedicine adoption. Compared to patients having in-person visits before the pandemic, patients having telemedicine visits during the pandemic achieved comparable improvements in daily opioid consumption, pain severity and interference, and physical health status. While telemedicine helped overcome many challenges faced by the patients, the limitations of telemedicine were also discussed. CONCLUSION: The COVID-19 pandemic stimulated the use of telemedicine. To facilitate telemedicine adoption beyond the pandemic, future research is needed to examine best practices for telemedicine adoption and provide additional evidence on the effectiveness of telemedicine.

Patient Experiences and Clinical Outcomes in a Multidisciplinary Perioperative Transitional Pain Service.

Siloed pain management across the perioperative period increases the risk of chronic opioid use and impedes postoperative recovery. Transitional perioperative pain services (TPSs) are innovative care models that coordinate multidisciplinary perioperative pain management to mitigate risks of chronic postoperative pain and opioid use. The objective of this study was to examine patients' experiences with and quality of recovery after participation in a TPS. Qualitative interviews were conducted with 26 patients from The Johns Hopkins Personalized Pain Program (PPP) an average of 33 months after their first PPP visit. A qualitative content analysis of the interview data showed that participants (1) valued pain expectation setting, individualized care, a trusting patient-physician relationship, and shared decision-making; (2) perceived psychiatric treatment of co-occurring depression, anxiety, and maladaptive behaviors as critical to recovery; and (3) successfully sustained opioid tapers and experienced improved functioning after PPP discharge. Areas for improved patient-centered care included increased patient education, specifically about the program, continuity of care with pain specialists while tapering opioids, and addressing the health determinants that impede access to pain care. The positive patient experiences and sustained clinical benefits for high-risk complex surgical patient support further efforts to implement and adapt similar models of perioperative pain care.

Patient engagement and prescription opioid use in perioperative pain management.

OBJECTIVE: To examine (1) patient perceptions regarding their engagement and the engagement of their families in perioperative pain management, (2) demographic and clinical characteristics associated with perceived patient and family engagement, and (3) the association between perceived patient and family engagement and patient outcomes. DESIGN: A prospective, observational study. SETTING: The Personalized Pain Program (PPP) at the Johns Hopkins Hospital in Baltimore, Maryland. PARTICIPANTS: Patients having more than one visit to the PPP. INTERVENTIONS: n/a. MAIN OUTCOME MEASURES: Since the inception of the PPP, patients were surveyed prior to each clinic visit to assess their pain severity and interference using the Brief Pain Inventory. Starting August 22, 2018, two additional questions were added to the survey to assess patient perceptions of their engagement and the engagement of their families in perioperative pain management. In addition, electronic medical records were reviewed to collect data on daily opioid consumption during the first and last PPP visits presurgery and post-surgery. RESULTS: The final analysis included 511 survey responses from 155 patients. Perceived engagement of the patient in perioperative pain management improved over time (p < .001) and was significantly associated with reduction in prescription opioid consumption after surgery (coef = 12.7, SE = 5.8, p = .031). CONCLUSIONS: Surgical patients and their family members should be actively engaged in perioperative pain management to improve prescription opioid use and the quality and safety of perioperative care.

Development of a staff recall system for mass casualty incidents using cell phone text messaging.

BACKGROUND: After a mass casualty incident (MCI), rapid mobilization of hospital personnel is required because of an expected surge of victims. Risk assessment of our department's manual phone tree recall system revealed multiple weaknesses that would limit an effective response. Because cell phone use is widespread within the department, we developed and tested a staff recall system, based in our anesthesia information management system (AIMS), using Short Message Service (SMS) text messaging. METHODS: We sent test text messages to anesthesia staff members' cell phone numbers, determined the distance from their home to the hospital, and stored this information in our AIMS. Latency testing for the time from transmission of SMS test messages from the server to return of an e-mail reply was determined at 2 different times on 2 different dates, 1 of which was a busy holiday weekend, using volunteers within the department. Two unannounced simulated disaster recall drills were conducted, with text messages sent asking for the anticipated time to return to the hospital. A timeline of available staff on site was determined. Reasons for failure to respond to the disaster notification message were tabulated. RESULTS: Latency data were fit by a log-normal distribution with an average of 82 seconds from message transmission to e-mail reply. Replies to the simulated disaster alert were received from approximately 50% of staff, with 16 projecting that they would have been able to be back at the hospital within 30 minutes on both dates. There would have been 21 and 23 staff in-house at 30 minutes, and 32 and 37 staff in-house at 60 minutes on the first and second test date, respectively, including in-house staff. Of the nonresponders to the alert, 48% indicated that their cell phone was not with them or was turned off, whereas 22% missed the message. CONCLUSIONS: Our SMS staff recall system is likely to be able to rapidly mobilize sufficient numbers of anesthesia personnel in response to an MCI, but actual performance cannot be predicted with confidence. Using our AIMS as the source for contact information and from which to send messages was simple, inexpensive, and easy to implement. Updating contact information, periodic testing, and analysis of responses to simulated disaster alerts are essential for the effective functioning of such a system. However, maintenance of alternative methods of communication is recommended, because there may be more significant message transmission delays and failures during an actual MCI, and not all staff will receive the text message in a timely fashion.

Addressing the Opioid Crisis One Surgical Patient at a Time: Outcomes of a Novel Perioperative Pain Program.

Opioid prescriptions in the surgical setting have been implicated as contributors to the opioid epidemic. The authors hypothesized that a multidisciplinary approach to perioperative pain management for patients on chronic opioid therapy could decrease postoperative opioid requirements while reducing postoperative pain scores and improving functional outcomes. Therefore, a Perioperative Pain Program (PPP) for chronic opioid users was implemented. This study presents outcomes from the first 9 months of the PPP. Sixty-one patients met the inclusion criteria. Opioid consumption in morphine milligram equivalent (MME) was calculated and physical and health status of patients was assessed with the Brief Pain Inventory, Short-Form McGill Pain Questionnaire, and Short Form-12. Preliminary results showed significant reduction in MME, improved pain scores, and improved function for surgical patients on chronic opioids. PPP effectively reduced opioid usage without negatively influencing patient-reported outcomes, such as physical pain score assessment and health-related quality of life.

An Innovative Perioperative Pain Program for Chronic Opioid Users: An Academic Medical Center's Response to the Opioid Crisis.

Increased utilization of prescription opioids for pain management has led to a nationwide public health crisis with alarming rates of addiction and opioid-related deaths. In the surgical setting, opioid prescriptions have been implicated as a contributing factor to the opioid epidemic. The authors developed an innovative model to address aspects of pain management and opioid utilization during preoperative evaluation, acute surgical hospitalization, and postoperative follow-up for chronic opioid users. This program involves multidisciplinary teams that include acute and chronic pain specialists, psychiatrists, integrative medicine specialists, and physical medicine and rehabilitation services. It also features a novel infrastructure for triage and pain management education and treatment. Individualized patient plans are devised that can include preoperative opioid weaning, regional anesthesia that minimizes opioid use, and multimodal techniques for surgical pain treatment. Multidisciplinary programs such as this have the potential to both improve perioperative pain control and prevent escalation of opioid use among chronic opioid users.

A model for an institutional response to the opioid crisis.

The use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. Physicians, policymakers, and researchers are focused on finding ways to decrease opioid use and overdose. This crisis calls for a coordinated response that includes the entire healthcare sector. In this work, the authors lay out a blueprint for such a response at the level of the academic medical center. The proposed model is a comprehensive opioid overdose prevention, response, and education program to evaluate, monitor, and address prescription opioid-related adverse events and addiction among all patients within a healthcare system. The approach includes three inter-related elements: (1) creation of an organizational structure that is subdivided into subcommittees to facilitate cross-functional collaboration and implementation. These subcommittees will focus on Research and Design, Implementation, Advisory, and Compliance with the recommendation. (2) Development of an effective communication plan throughout the institution to enable the organization to function seamlessly and efficiently as a single unit, (3) development of a data tracking and reporting system that intended to have a 360° view of all aspects of opioid prescription and downstream patient outcomes. The most effective response system will require an organizational structure that facilitates the ad hoc constitution of cross-functional teams with members drawn from all levels of the organizational hierarchy (executive leadership to frontline staff). Such a structure provides the teams with immediate solutions as developed by the frontline staff and authority to remove institutional barriers that may delay or limit the successful implementation. The model described was developed in our institution by a cross-functional team that included members from the Johns Hopkins School of Medicine and Johns Hopkins University Carey Business School, Department of Operations Management. The multidisciplinary nature of collaboration allowed us to develop a model for an immediate institution-wide response to the opioid crisis, and one that other healthcare organizations could adopt with local modification as a template for execution. The model also meant to serve as a template for an institutional rapid-response that can be seamlessly implemented during any future drug-related crisis or epidemic.

Electrical stimulation of low-threshold afferent fibers induces a prolonged synaptic depression in lamina II dorsal horn neurons to high-threshold afferent inputs in mice.

Electrical stimulation of low-threshold Aß-fibers (Aß-ES) is used clinically to treat neuropathic pain conditions that are refractory to pharmacotherapy. However, it is unclear how Aß-ES modulates synaptic responses to high-threshold afferent inputs (C-, Aδ-fibers) in superficial dorsal horn. Substantia gelatinosa (SG) (lamina II) neurons are important for relaying and modulating converging spinal nociceptive inputs. We recorded C-fiber-evoked excitatory postsynaptic currents (eEPSCs) in spinal cord slices in response to paired-pulse test stimulation (500 µA, 0.1 millisecond, 400 milliseconds apart). We showed that 50-Hz and 1000-Hz, but not 4-Hz, Aß-ES (10 µA, 0.1 millisecond, 5 minutes) induced prolonged inhibition of C-fiber eEPSCs in SG neurons in naive mice. Furthermore, 50-Hz Aß-ES inhibited both monosynaptic and polysynaptic forms of C-fiber eEPSC in naive mice and mice that had undergone spinal nerve ligation (SNL). The paired-pulse ratio (amplitude second eEPSC/first eEPSC) increased only in naive mice after 50-Hz Aß-ES, suggesting that Aß-ES may inhibit SG neurons by different mechanisms under naive and nerve-injured conditions. Finally, 50-Hz Aß-ES inhibited both glutamatergic excitatory and GABAergic inhibitory interneurons, which were identified by fluorescence in vGlut2-Td and glutamic acid decarboxylase-green fluorescent protein transgenic mice after SNL. These findings show that activities in Aß-fibers lead to frequency-dependent depression of synaptic transmission in SG neurons in response to peripheral noxious inputs. However, 50-Hz Aß-ES failed to induce cell-type-selective inhibition in SG neurons. The physiologic implication of this novel form of synaptic depression for pain modulation by Aß-ES warrants further investigation.

MrgC agonism at central terminals of primary sensory neurons inhibits neuropathic pain.

Chronic neuropathic pain is often refractory to current pharmacotherapies. The rodent Mas-related G-protein-coupled receptor subtype C (MrgC) shares substantial homogeneity with its human homologue, MrgX1, and is located specifically in small-diameter dorsal root ganglion neurons. However, evidence regarding the role of MrgC in chronic pain conditions has been disparate and inconsistent. Accordingly, the therapeutic value of MrgX1 as a target for pain treatment in humans remains uncertain. Here, we found that intrathecal injection of BAM8-22 (a 15-amino acid peptide MrgC agonist) and JHU58 (a novel dipeptide MrgC agonist) inhibited both mechanical and heat hypersensitivity in rats after an L5 spinal nerve ligation (SNL). Intrathecal JHU58-induced pain inhibition was dose dependent in SNL rats. Importantly, drug efficacy was lost in Mrg-cluster gene knockout (Mrg KO) mice and was blocked by gene silencing with intrathecal MrgC siRNA and by a selective MrgC receptor antagonist in SNL rats, suggesting that the drug action is MrgC dependent. Further, in a mouse model of trigeminal neuropathic pain, microinjection of JHU58 into ipsilateral subnucleus caudalis inhibited mechanical hypersensitivity in wild-type but not Mrg KO mice. Finally, JHU58 attenuated the miniature excitatory postsynaptic currents frequency both in medullary dorsal horn neurons of mice after trigeminal nerve injury and in lumbar spinal dorsal horn neurons of mice after SNL. We provide multiple lines of evidence that MrgC agonism at spinal but not peripheral sites may constitute a novel pain inhibitory mechanism that involves inhibition of peripheral excitatory inputs onto postsynaptic dorsal horn neurons in different rodent models of neuropathic pain.

Tolerance develops to the antiallodynic effects of the peripherally acting opioid loperamide hydrochloride in nerve-injured rats.

Peripherally acting opioids are potentially attractive drugs for the clinical management of certain chronic pain states due to the lack of centrally mediated adverse effects. However, it remains unclear whether tolerance develops to peripheral opioid analgesic effects under neuropathic pain conditions. We subjected rats to L5 spinal nerve ligation (SNL) and examined the analgesic effects of repetitive systemic and local administration of loperamide hydrochloride, a peripherally acting opioid agonist. We found that the inhibition of mechanical hypersensitivity, an important manifestation of neuropathic pain, by systemic loperamide (1.5mg/kg subcutaneously) decreased after repetitive drug treatment (tolerance-inducing dose: 0.75 to 6.0mg/kg subcutaneously). Similarly, repeated intraplantar injection of loperamide (150 µg/50 µL intraplantarly) and D-Ala(2)-MePhe(4)-Glyol(5) enkephalin (300 µg/50 µL), a highly selective mu-opioid receptor (MOR) agonist, also resulted in decreased inhibition of mechanical hypersensitivity. Pretreatment with naltrexone hydrochloride (5mg/kg intraperitoneally) and MK-801 (0.2mg/kg intraperitoneally) attenuated systemic loperamide tolerance. Western blot analysis showed that repetitive systemic administration of morphine (3mg/kg subcutaneously), but not loperamide (3mg/kg subcutaneously) or saline, significantly increased MOR phosphorylation in the spinal cord of SNL rats. In cultured rat dorsal root ganglion neurons, loperamide dose-dependently inhibited KCl-induced increases in [Ca(2+)]i. However, this drug effect significantly decreased in cells pretreated with loperamide (3 µM, 72 hours). Intriguingly, in loperamide-tolerant cells, the delta-opioid receptor antagonist naltrindole restored loperamide's inhibition of KCl-elicited [Ca(2+)]i increase. Our findings indicate that animals with neuropathic pain may develop acute tolerance to the antiallodynic effects of peripherally acting opioids after repetitive systemic and local drug administration.