Ariana Nelson

Opioid-induced decreases in rat brain adenosine levels are reversed by inhibiting adenosine deaminase

Background:Opioids disrupt sleep and adenosine promotes sleep, but no studies have characterized the effects of opioids on adenosine levels in brain regions known to regulate states of arousal. Delivering opioids to the pontine reticular formation (PRF) and substantia innominata (SI) region of the basal forebrain disrupts sleep. In contrast, administering adenosine agonists to the PRF or SI increases sleep. These findings encouraged the current study testing the hypothesis that microdialysis delivery of opioids to the PRF or SI decreases adenosine levels in the PRF or SI, respectively. Methods:A microdialysis probe was placed in the PRF of isoflurane anesthetized rats and perfused with Ringers solution (control) followed by Ringers solution containing morphine (0, 10, 30, 100, or 300 μm), fentanyl (100 μm), morphine (100 μm) and the adenosine deaminase inhibitor EHNA (100 μm), or naloxone (10 μm) and morphine (100 μm). Additional experiments measured adenosine levels in the SI before and during microdialysis delivery of morphine, fentanyl, and morphine plus EHNA. Results:Morphine caused a significant (P < 0.05) concentration-dependent decrease in PRF adenosine levels. The significant decrease (−20%) in adenosine caused by 100 μm morphine was blocked by coadministration of naloxone. Fentanyl also significantly decreased (−13.3%) PRF adenosine. SI adenosine levels were decreased by morphine (−26.8%) and fentanyl (−27.4%). In both PRF and SI, coadministration of morphine and EHNA prevented the significant decrease in adenosine levels caused by morphine alone. Conclusions:These data support the interpretation that decreased adenosine levels in sleep-regulating brain regions may be one of the mechanisms by which opioids disrupt sleep.

The Incidence and Severity of Physical Pain Symptoms in Marfan Syndrome: A Survey of 993 Patients.

Objective:To characterize the incidence, severity, quality, and treatment of pain in a large cohort of Marfan patients. Materials and Methods:A web-based survey was distributed to all individuals on the Marfan Foundation listserv. Respondents who endorsed a diagnosis of Marfan syndrome were queried as to the presence, frequency, severity, location, and quality of their pain and were asked to describe the specific treatments used to manage pain. The primary outcome was the presence of pain symptoms in respondents during the 7-day period preceding completion of the survey. Results:Of the 993 patients with a verified diagnosis of Marfan syndrome, 67% (95% confidence interval, 64%-69%) reported pain in the preceding 7 days. Median (interquartile range) “average daily pain” was 4 (3 to 5) on the numeric rating scale; “worst pain” was 7 (5 to 8). “Worst pain experienced” was ≥4 in 93% of respondents. Analgesic use to control pain related to Marfan syndrome was reported in 56% of respondents with 55% reporting <50% pain relief with this modality. Few patients underwent interventional procedures for pain control, despite intractable back and joint pain being common. A majority (52%) of respondents rated “chronic pain care” from their physicians as either “poor” or “fair.” Discussion:Our findings suggest that pain symptoms in Marfan patients are underestimated and likely undertreated. We propose a need for improved patient and medical provider awareness of pain management options in this population, including the development of effective algorithms to treat pain in Marfan patients.

A Prospective Randomized Comparative Trial of Targeted Steroid Injection Via Epidural Catheter Versus Standard C7-T1 Interlaminar Approach for the Treatment of Unilateral Cervical Radicular Pain.

Background and Objectives No study has compared cervical interlaminar epidural steroid injection (CIESI) with epidural catheter advancement to the side and level of pathology versus standard C7-T1 CIESI. This study investigated whether cervical radicular pain is more effectively treated by CIESI with a targeted epidural catheter versus a standard C7-T1 approach. Methods Prospective, randomized, single-blinded trial. Primary outcome: Numerical Rating Scale (NRS) pain at 1 month. Secondary outcomes: Oswestry Neck Disability Index (ONDI), Pain Disability Index (PDI), McGill Pain Questionnaire (MPQ), Patient Global Impression of Change (PGIC), daily morphine equivalents (DME), and Medication Quantification Scale (MQS) III scores. Results Seventy-six participants with a median age of 48 years (IQR, 40–56 years), 59% female, with C4 (n = 2), C5 (n = 27), or C6 (n = 47) radicular pain were enrolled. At 1 month in the catheter and no catheter groups, respectively: 26 (72%, 95% confidence interval [CI], 57%–87%) and 23 (60%; 95% CI, 45%–75%) participants reported 50% or greater NRS reduction; 24 (67%; 95% CI, 52%–84%) and 23 (58%; 95% CI, 42%–73%) participants reported 30% or greater ONDI reduction. There were no group differences in median NRS, ONDI, PDI, MPQ, PGIC, DME, or MQSIII scores (P > 0.05). Intergroup differences were not observed at any follow-up interval. Conclusions This trial showed no significant difference in clinical outcomes with CIESI using a targeted epidural catheter compared to a standard C7-T1 approach for the treatment of unilateral cervical radicular pain at the C5 or C6 level. Both techniques were associated with clinically meaningful improvement across outcome domains of pain, function, disability, and medication use. These effects persisted to 6-month follow-up. The study was registered at Clinical Trials.gov (NCT02095197).

Efficacy of Pregabalin in the Treatment of Radicular Pain: Results of a Controlled Trial

Background: Pregabalin is commonly used to treat patients with various neuropathic pain syndromes. Objectives: The purpose of the present study was to evaluate the efficacy of pregabalin in patients with lumbar or cervical radicular pain. Patients and Methods: A prospective, randomized, double-blind trial was conducted in 39 patients with lumbar and cervical radicular pain, who received 3 weeks of either pregabalin (n = 10) or placebo (n = 9) treatment. Baseline pain and disability were evaluated before the treatment and were re-evaluated, along with overall patient satisfaction, after the 3 weeks of treatment. Results: Data on 19 of the 39 patients recruited were available for analysis. No statistically significant differences in the pain, disability, and patient satisfaction scores were found between the groups. When the individual patient scores were assessed, the placebo treatment was found to be efficacious in 4 of the 9 patients and pregabalin was effective in 2 of the 10 patients, but the difference was not statistically significant (P = 0.350). Conclusions: The present data do not suggest that pregabalin is more efficacious than placebo in the treatment of lumbar and cervical radicular pain. However, the small sample size of this study may have affected the ability to detect such a difference.

Does cervical interlaminar epidural steroid injection with low-dose lidocaine cause objective upper extremity weakness? A preliminary study

Objective Low-dose local anesthetic is often used in cervical interlaminar epidural steroid injections (CIESI), yet its effect on upper extremity strength has not been studied. The presence of consequent weakness has potential implications for postprocedure safety. This study aimed to determine whether low-dose lidocaine in a C7-T1 CIESI causes objective weakness. Design Prospective case series. Setting Academic pain center. Subjects Adults, cervical radicular pain. Methods Participants underwent CIESI with 1 mL of 1% lidocaine (3 mL total injectate). Elbow flexion (EF), wrist extension (WE), elbow extension (EE), and handgrip strength were measured by dynamometry at baseline, 15 minutes, and 30 minutes postinjection. Changes in strength from baseline and the proportion of participants with a minimum perceptible change in EF, WE, EE, and handgrip strength (≥20%) and 95% confidence intervals (CIs) were calculated. Results Twenty-seven participants were included. At 15 and 30 minutes postinjection, there was no within-participant difference in EF, WE, EE, and handgrip strength from baseline overall. Nonetheless, five (19%, 95% CI = 4-33) of the participants demonstrated a 20% or greater strength decrease in at least one myotomal distribution. A 20% or greater decrease in strength was present in left EF 4% (95% CI = 0-11%), right EF 7% (95% CI = 0-17%), left WE 4% (95% CI = 0-11%), and right WE 7% (95% CI = 0-17%). Conclusions The present data suggest that CIESI with an injectate volume of 3 mL that includes 1 mL of 1% lidocaine may result in objective upper extremity weakness that is above the minimum threshold of perception in a subset of patients.

Deep Muscle Injections: Piriformis, Scalene Muscle, Iliopsoas Injections

Abstract Pain syndromes that can be attributed to deep muscles are often caused by mechanical impingement of the muscular tissue upon traversing neurovascular structures. The most common of these disorders include piriformis syndrome, in which the piriformis muscle may compress the sciatic nerve, and thoracic outlet syndrome (TOS), in which the scalene musculature compresses the brachial plexus. In contrast, iliopsoas-related pain is not related to compression or irritation of the nerve. However, all three of these pathophysiologic states can be managed through conservative measures, injection therapy, or surgical intervention. Conservative measures typically include multimodal treatment with antiinflammatory analgesics, muscle relaxants, and physical therapy. If these fail, injections of local anesthetic, steroid, or botulinum toxin into the muscles causing irritation are often a second-line option. Surgery is typically reserved for refractory cases with significant negative impact upon a patient’s functional status.

Use of occipital nerve block in emergency department treatment of status migrainosus

Migraine headaches make up a significant proportion of emergency department visits. There are multiple pharmacologic treatment modalities for migraine abortive therapy; however, these treatments are rarely targeted to the precise area of pain and thus elicit multiple systemic effects. It has been well established in the anesthesia pain literature that occipital nerve blocks can provide not only immediate pain relief from occipital migraines, but can also result in a long-term resolution of occipital migraines. In this case report, we present how an occipital nerve block in the emergency department resulted in immediate and long-lasting resolution of a patients occipital migraine.

Disease-modifying Antirheumatic Drugs for the Treatment of Low Back Pain: A Systematic Review of the Literature

Low back pain (LBP) is a common source of pain and disability, which has an enormous adverse impact on affected individuals and the community as a whole. The etiologies of LBP are protean and local inflammation contributes to the majority of these processes. Although an array of potent disease‐modifying anti‐rheumatic drugs (DMARDs), which are typically anti‐inflammatory in character, have become clinically available only corticosteroids are routinely used for the treatment of LBP. To further investigate this potentially underutilized therapy, we reviewed the available literature to determine the role of DMARDs in the treatment of LBP. Our results show that the current DMARD use for LBP is indeed limited in scope and is characterized by isolated use and empiric selection of drugs from a range of available DMARDs. Moreover, the dose, frequency, and route of drug administration are selected arbitrarily and deviated from treatment protocols proposed for the management of other inflammatory conditions. The literature published on this topic is of low quality, and the results of the reviewed trials were inconclusive or demonstrated only short‐term efficacy of these medications. Based on the findings of this review, we recommend that the future DMARD use for LBP is initially limited to patients with debilitating disease who are unresponsive to conventional treatments, and the criteria for drug selection and routes of drug administration are clearly defined and may be modeled after treatment protocols for other inflammatory conditions.