Stellate Ganglion Block for the Treatment of COVID-19-Induced Olfactory Dysfunction: A Prospective Pilot Study.

OBJECTIVE: The objective of this study was to explore the safety and feasibility of stellate ganglion blocks (SGBs) to treat persistent COVID-19-induced olfactory dysfunction (OD). Secondarily, the goal was to determine effect sizes to plan a future randomized clinical trial. STUDY DESIGN: Prospective case series. SETTING: Quaternary Care Academic Medical Center. METHODS: In this single-arm pilot trial, adult participants with a COVID-19 diagnosis ≥ 12 months prior to enrollment with OD underwent bilateral SGBs. Subjects were followed for 1 month after completion of SGB. The primary outcome measure was the change in the Clinical Global Impression-Improvement Scale for smell loss. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Olfactory Dysfunction Outcomes Rating (ODOR). RESULTS: Twenty participants were enrolled with a mean (SD) age of 46 (11) years and a mean (SD) duration of OD of 21 (5) months. At 1 month, 10 (50%) participants experienced at least slight subjective improvement in their OD, 11 (55%) attained a clinically meaningful improvement in smell identification using the UPSIT, and 7 (35%) achieved a clinically meaningful improvement in olfactory-specific quality of life (QoL) measured by the ODOR. The median difference between UPSIT scores at baseline and 1 month was 6 (95% confidence interval: 3-11), exceeding the minimal clinically important difference of 4. There were no serious adverse events. CONCLUSION: Sequential SGBs for COVID-19-associated OD were safe and associated with modest improvements in subjective olfaction, odor identification, and olfactory-specific QoL. A placebo-controlled trial is warranted to determine the efficacy of SGBs for COVID-19-associated OD.

Decompression with Brachioradialis Tenotomy Improves Pain and Quality of Life in Patients with Radial Sensory Nerve Compression.

BACKGROUND: Decompression of the superficial sensory branch of the radial nerve (SBRN) with complete brachioradialis tenotomy may treat pain in both simple and complex cases of SBRN compression neuropathy. METHODS: A retrospective chart review was performed of consecutive patients undergoing this procedure between 2008 and 2020 including postoperative outcomes within 90 days. Data were collected and analyzed, including patient and injury demographics, pain descriptors, and patient-reported pain questionnaire, including reported pain severity and impact on quality of life using visual analogue scale (VAS) instruments. Within-group presurgical and postsurgical analyses and between-group statistical analyses were performed. RESULTS: Thirty-three of 58 patients met inclusion criteria. Median time from symptom onset to surgery was 300 days, and median postoperative follow-up time was 37 days. Twenty-five percent of patients ( n = 8) underwent isolated SBRN decompression. The remainder had concomitant decompression of another radial [ n = 16 (48%) or peripheral [ n = 12 (36%)] entrapment point. Ten of 33 patients (30%) had resolution of pain at final follow-up ( P = 0.004). Median change in worst pain over the previous week was -4 ( P < 0.001), and average pain over the last month was -2.75 ( P < 0.001) on the VAS. The impact of pain on quality of life showed a median change of -3 ( P < 0.001) on the VAS. CONCLUSION: Decompression of the sensory branch of the radial nerve including a complete brachioradialis tenotomy improves pain and quality-of-life VAS scores in patients with both simple compression neuropathy syndrome and complex nerve compression syndrome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

What is Operative? Conceptualizing Neuralgia: Neuroma, Compression Neuropathy, Painful Hyperalgesia, and Phantom Nerve Pain.

Neuralgia, or nerve pain, is a common presenting complaint for the hand surgeon. When the nerve at play is easily localized, and the cause of the pain is clear (eg, carpal tunnel syndrome), the patient may be easily treated with excellent results. However, in more complex cases, the underlying pathophysiology and cause of neuralgia can be more difficult to interpret; if incorrectly managed, this leads to frustration for both the patient and surgeon. Here we offer a way to conceptualize neuralgia into 4 categories-compression neuropathy, neuroma, painful hyperalgesia, and phantom nerve pain-and offer an illustrative clinical vignette and strategies for optimal management of each. Further, we delineate the reasons why compression neuropathy and neuroma are amenable to surgery, while painful hyperalgesia and phantom nerve pain are not.

Quality of Life and Psychosocial Factors as Predictors of Pain Relief Following Nerve Surgery.

Background: Peripheral nerve injuries may result in pain, disability, and decreased quality of life (QoL). Pain is an incompletely understood experience and is associated with emotional and behavioral qualities. We hypothesized that pain following peripheral nerve surgery could be predicted by changes in emotions or QoL postoperatively. Methods: Using prospectively collected data, a retrospective study design was used to evaluate the relationships among pain, QoL, and psychosocial factors in patients who underwent peripheral nerve surgery. Patients completed questionnaires rating pain; impact of pain on QoL, sadness, depression, frustration, anger, and hopefulness before surgery; and each postoperative follow-up visit. Multilevel modeling was used to assess the concurrent and lagged relationships between pain and psychosocial factors. Results: Increased pain was concurrently associated with decreased hopefulness (P = .001) and increased the impact on QoL, sadness, depression, and anger (P < .001). In lagged analyses, the impact on QoL and anger prospectively predicted pain (P < .001 and P = .02, respectively). Pain predicted subsequent scores of QoL, sadness, depression, anger, and hopefulness (P < .01). Having an upper limb nerve injury and self-report of "no comment for childhood trauma" were predictors of postsurgical pain. Conclusion: Psychosocial measures and pain are reciprocally related among patients who underwent surgery for peripheral nerve injuries or compression. Our study provides evidence of the important relationships among psychosocial factors, pain, and outcome and identifies treatment targets following nerve surgery.

Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception.

BACKGROUND: Interstitial cystitis/painful bladder syndrome (IC/PBS), is a severely debilitating chronic condition that is frequently unresponsive to conventional pain medications. The etiology is unknown, however evidence suggests that nervous system sensitization contributes to enhanced pain in IC/PBS. In particular, central nervous system plasticity of glutamatergic signaling involving NMDA and metabotropic glutamate receptors (mGluRs) has been implicated in a variety of chronic pain conditions. Here, we test the hypothesis that mGluR5 mediates both non-inflammatory and inflammatory bladder pain or nociception in a mouse model by monitoring the visceromotor response (VMR) during graded bladder distention. RESULTS: Using a combination of genetic and pharmacologic approaches, we provide evidence indicating that mGluR5 is necessary for the full expression of VMR in response to bladder distention in the absence of inflammation. Furthermore, we observed that mice infected with a uropathogenic strain of Escherichia coli (UPEC) develop inflammatory hyperalgesia to bladder distention, and that the selective mGluR5 antagonist fenobam [N-(3-chlorophenyl)-N'-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2-yl) urea], reduces the VMR to bladder distention in UPEC-infected mice. CONCLUSIONS: Taken together, these data suggest that mGluR5 modulates both inflammatory and non-inflammatory bladder nociception, and highlight the therapeutic potential for mGluR5 antagonists in the alleviation of bladder pain.

PAF-receptor antagonists, lovastatin, and the PTK inhibitor genistein inhibit H2O2 secretion by macrophages cultured on oxidized-LDL matrices.

Adhesion of mononuclear phagocytes (Macs) to extracellular matrices containing oxidized low-density lipoproteins (oxLDL) stimulates these cells to secrete reactive oxygen species (e.g., O2-, H2O2) that are believed to promote atherogenesis. Current in vitro systems designed to measure Mac H2O2 secretion in response to oxLDL show that these cells secrete H2O2 for only a few hours after plating. The slow onset and chronicity of atherogenesis, however, suggested to us that Mac ROS secretion might be sustained for much longer periods when Macs are maintained in an environment resembling that in the intima of arteries undergoing atherogenesis. The findings reported here confirm this suggestion. They show that Macs maintained on collagen IV matrices containing oxLDL in medium containing human plasma-derived serum secrete H2O2 continuously and in large amounts for at least 11 days. Using this system we tested the effects of compounds known to attenuate atherogenesis in vivo. Platelet-activating factor (PAF) receptor antagonists, lovastatin, and the isoflavone protein tyrosine kinase (PTK) inhibitor genistein each reduced H2O2 secretion by Macs maintained on oxLDL-containing matrices by approximately 60%. Lovastatin's inhibitory effect was blocked completely by addition of geranylgeranyl pyrophosphate to the medium. We conclude that matrix-bound and oxidized lipoproteins stimulate Macs to produce H2O2 continuously and in large quantities via a pathway that involves PAF receptors and PTK and is reversibly blocked by inhibitors of protein prenylation.