Radiotracers in the Diagnosis of Pain: A Mini Review.

The diagnosis and understanding of pain is challenging in clinical practice. Assessing pain relies heavily on self-reporting by patients, rendering it inherently subjective. Traditional clinical imaging methods such as computed tomography and magnetic resonance imaging can only detect anatomical abnormalities, offering limited sensitivity and specificity in identifying pain-causing conditions. Radiotracers play a vital role in molecular imaging that aims to identify abnormal biological processes at the cellular level, even in apparently normal anatomical structures. Therefore, molecular imaging is an important area of research as a prospective diagnostic modality for pain-causing pathophysiology. We present a mini review of the current knowledge base regarding radiotracers for identification of pain in vivo. We also describe radiocaine, a novel positron emission tomography imaging agent for sodium channels that has shown great potential for identifying/labeling pain-producing nerves and producing an objectively measurable pain intensity signal.

Defining Personas of People Living with Chronic Pain: An Ethnographic Research Study.

Introduction: Pain is the leading reason for which people seek medical care in the United States, and chronic pain (CP) affects approximately 50 million people in the US Pain perception is deeply personal, is highly correlated with behavioral and emotional disorders, and is greatly influenced by physiological and environmental factors. The patient-provider relationship can have profound implications for clinical outcomes within the context of treating CP. However, limited access to pain specialists, the complex nature of many CP-causing conditions, the absence of instruments for objective pain measurement, and the need to foster a trust-based patient-provider relationship throughout treatment pose unique challenges. Objective: To support a more optimal CP care delivery system that leverages a healthy therapeutic patient-provider relationship, we systematically gathered deeper knowledge of the behaviors, interpersonal dynamics, home environment, values, and mindsets of people who experience CP. Methods: We employed ethnographic research methods to collect and analyze data on views, habits, strategies, attitudes, and life circumstances of a range of participants living with CP. We aggregated, analyzed, and summarized participant data to identify trends and similarities. Results: Our findings suggest that patients can be broadly categorized into five predominant pain typologies, or "personas", which are characterized by respective symptom durations, care management preferences, values, communication styles, and behaviors. Conclusion: Identifying CP personas may enhance the ability to personalize CP care and help foster more robust therapeutic relationships, which may lead to greater trust, improved patient satisfaction, and better clinical outcomes.

Point To Area of Pain: A Clinically Useful Telehealth Physical Exam Technique for Focal Nociceptive and Neuropathic Pain.

BACKGROUND: Chronic pain is a leading cause of disease burden and disability globally. The COVID-19 pandemic catalyzed a major paradigm shift in health care delivery with the universal adoption of telemedicine. Telehealth physical examination is particularly challenging and little guidance is available on this topic. OBJECTIVES: We attempt to describe the Point To the Area of Pain (PTAP) test and establish a consensus regarding its utility for musculoskeletal examination (MSK) via telehealth. STUDY DESIGN: The authors drafted an online survey. SETTING: The survey was sent to physicians and nurse practitioners within the authors' respective departments and institutions who routinely use telemedicine to treat pain METHODS: Respondents (n = 61) were asked about their primary specialty, comfort level in evaluating patients in pain, use of the PTAP test and its perceived clinical relevance to patient management, and other relevant questions. RESULTS: Respondents were predominantly trained in Physiatry (47.5%), Anesthesiology (23%), Neurology (13.1%) and Family Medicine (11.5%); 67.2% of providers treat pain related diseases > 75% of the time; 50.8% of respondents were "somewhat comfortable" at performing a virtual MSK exam and 29.5% were "not comfortable"; 65.5% utilize the PTAP test and 88.5% agree or strongly agree that this test provides extrinsic clinically relevant information. LIMITATIONS: The relatively small number of respondents. CONCLUSION: PTAP tests should not replace the standard accepted in-person or virtual physical examination in practice, but in the absence of a hands-on exam, the PTAP test is a clear and concise test that can easily be performed in conjunction with other techniques via telehealth, and in the context of assessing pain provides useful clinical information that can help guide medical decision making.

Acute Cauda Equina Syndrome Due to Spondylolisthesis in the Midst of a Pandemic: A Case Report.

CASE: A 54-year-old woman with chronic lumbar radiculopathy due to grade II spondylolisthesis at lumbar 4 to 5 developed acute cauda equina syndrome (CES) after an elective lumbar decompression, and fusion was delayed because of statewide bans on elective procedures during the pandemic. The diagnosis was made largely through telehealth consultation and eventually prompted urgent neurosurgical intervention. CONCLUSION: This case report illustrates a rare presentation of acute CES and highlights some of the challenges of practicing clinical medicine in the midst of a pandemic.

Chronic Low Back Pain: The Therapeutic Benefits of Diagnostic Medial Branch Nerve Blocks.

BACKGROUND: Chronic low back pain (CLBP) is an extremely prevalent disease, whose etiology is often multifactorial. Facet joint arthropathy is one of the most common causes of CLBP. Facet joints are innervated by the medial branches of the primary and adjacent level dorsal rami and are, therefore, key potential targets for the symptomatic management of CLBP. A lumbar medial branch nerve block (MBB) procedure is often used to assist in the diagnosis of facet mediated CLBP. For unclear reasons, some patients experience protracted relief of CLBP after diagnostic MBBs alone. OBJECTIVE: To describe the phenomenon of protracted relief of CLBP after diagnostic MBBs and search for predictors of this response. STUDY DESIGN: A retrospective chart review of patients who underwent MBB procedures by a single practitioner, over a 2 year period, was conducted. SETTING: All patients were seen at the Montefiore Multidisciplinary Pain Program, Bronx, NY. METHODS: Data from follow up visits was used to categorize patient's response to MBBs as having no relief (NR), transient relief (TR) or protracted relief (PR). Patient demographics and characteristics were collected, and a multivariate analysis investigating associations with PR was conducted. RESULTS: 146 patients met inclusion criteria. 41 patients (28%) had NR, 54 (37%) had TR, and 51 (35%) had PR. CLBP symptom duration of < 6 months (P = 0.013) and unilateral back pain symptoms (P = 0.0253) were significantly associated with PR after MBB. LIMITATION: This is a retrospective study with a relatively small sample size conducted on patients belonging to a single practitioner. Outcomes were based largely on subjective patient satisfaction scores. CONCLUSIONS: In select patients, MBB may produce protracted relief of CLBP symptoms. The authors present distinct hypotheses which may help explain the therapeutic effects of diagnostic MBB procedures.

Expanding frontiers in telehealth: Video assisted at-home application of capsaicin 8% patch.

In recent years, the delivery of health services has undergone a major paradigm shift towards expanded outpatient services and widespread use of telemedicine. Post-herpetic neuralgia (PHN) is a treatment recalcitrant neuropathic pain condition referring to pain persisting more than three months from the initial onset of an acute herpes zoster. QUTENZA® (capsaicin 8% patch) is a single 1-hr localized treatment for PHN and can provide several months of pain relief per application. However, patient access to capsaicin 8% patch is limited due to sensitive handling protocols that require the patch application to occur under physicians or healthcare professionals under the close supervision of a physician. Herein, we describe a successful treatment of PHN at-home, using capsaicin 8% patch, performed under full supervision and instruction from a physician using video telehealth services. SIGNIFICANCE: This is a case report of the successful treatment of post-herpetic neuralgia at-home using Capsaicin 8% patch. The procedure was performed under full supervision and instruction from a physician using video telehealth services. Not only did the patient tolerate the procedure and have significant efficacy, she voiced preference to repeat treatment in this manner versus going back to the office.

The Other Side of the COVID-19 Curve: A Model for the Safe Reintegration of Elective Interventional Pain Procedures.

BACKGROUND: Throughout the COVID-19 pandemic, clinicians have had to think quickly, adapt to changing recommendations sometimes on a daily basis, and have often had to rely on trial-and-error-based treatment protocols under various conditions. As we move on past the apex of the COVID-19 curve, new treatment protocols for the safe reintegration of elective interventional pain procedures into chronic pain practice are needed. METHODS: Literature review and description of a model for the safe reintegration of interventional pain procedures. LIMITATIONS: A narrative review with paucity of literature. DISCUSSION: Herein we describe one such model in the hopes that through similar knowledge sharing, we can draw on others experiences to reach a collective conclusion on the safest, most effective, and efficient way(s) to move forward.

Needle-Through-Needle Technique in Lumbar Interlaminar Epidural Steroid Injection: A Case Report.

When performing lumbar epidural steroid injection on obese patients, needle placement can be challenging due to the difficulty in estimating the appropriate needle length to utilize. Often times, the standard 3.5-inch Tuohy needle is too short to reach its target. In our case report, a needle-through-needle technique was attempted in a lumbar interlaminar epidural steroid injection procedure after the initial needle fell short of the epidural space. To avoid removing the initial needle and restarting the procedure using a longer needle, a 20-gauge 6-inch Tuohy needle was inserted into the 17-gauge 3.5-inch Tuohy needle, successfully reaching the epidural space. This technique can facilitate quicker needle placement by avoiding the need for restarting the procedure with a longer needle. Thus, procedural time and radiation exposure may be decreased, as may patient discomfort from repeat needle insertions.

Peripheral Nerve Blocks for the Treatment of Headache in Older Adults: A Retrospective Study.

OBJECTIVE: The objective of this study is to provide demographical and clinical descriptions of patients age 65 years old and older who were treated with peripheral nerve blocks (PNBs) at our institution and evaluate the safety and efficacy of this treatment. BACKGROUND: Headache disorders are common, disabling chronic neurological diseases that often persist with advancing age. Geriatric headache management poses unique therapeutic challenges because of considerations of comorbidity, drug interactions, and adverse effects. Peripheral nerve blocks are commonly used for acute and short-term prophylactic treatment for headache disorders and may be a safer alternative to standard pharmacotherapy in this demographic. DESIGN: We performed a single center, retrospective chart review of patients at least 65 years of age who received peripheral nerve blocks for headache management over a 6 year period. RESULTS: Sixty-four patients were mostly female (78%) with an average age of 71 years (range 65-94). Representative headache diagnoses were chronic migraine 50%, episodic migraine 12.5%, trigeminal autonomic cephalalgia 9.4%, and occipital neuralgia 7.8%. Average number of headache days/month was 23. Common comorbidities were hypertension 48%, hyperlipidemia 42%, arthritis 27%, depression 47%, and anxiety 33%. Eighty-nine percent were prescribed at least 1 medication fulfilling the Beers criteria. The average number of peripheral nerve blocks per patient was 4. Peripheral nerve blocks were felt to be effective in 73% for all headaches, 81% for chronic migraine, 75% for episodic migraine, 67% for chronic tension type headache, 67% for new daily persistent headache, and 60% for occipital neuralgia. There were no adverse events related to PNBs reported. CONCLUSIONS: PNBs might be a safe and effective alternative headache management strategy for older adults. Medical and psychiatric comorbidities, medication overuse, and Beers list medication rates were extraordinarily high, giving credence to the use of peripherally administered therapies in the geriatric population that may be better tolerated and safer.

Schizophrenia-like features in transgenic mice overexpressing human HO-1 in the astrocytic compartment.

Delineation of key molecules that act epigenetically to transduce diverse stressors into established patterns of disease would facilitate the advent of preventive and disease-modifying therapeutics for a host of neurological disorders. Herein, we demonstrate that selective overexpression of the stress protein heme oxygenase-1 (HO-1) in astrocytes of novel GFAP.HMOX1 transgenic mice results in subcortical oxidative stress and mitochondrial damage/autophagy; diminished neuronal reelin content (males); induction of Nurr1 and Pitx3 with attendant suppression of their targeting miRNAs, 145 and 133b; increased tyrosine hydroxylase and α-synuclein expression with downregulation of the targeting miR-7b of the latter; augmented dopamine and serotonin levels in basal ganglia; reduced D1 receptor binding in nucleus accumbens; axodendritic pathology and altered hippocampal cytoarchitectonics; impaired neurovascular coupling; attenuated prepulse inhibition (males); and hyperkinetic behavior. The GFAP.HMOX1 neurophenotype bears resemblances to human schizophrenia and other neurodevelopmental conditions and implicates glial HO-1 as a prime transducer of inimical (endogenous and environmental) influences on the development of monoaminergic circuitry. Containment of the glial HO-1 response to noxious stimuli at strategic points of the life cycle may afford novel opportunities for the effective management of human neurodevelopmental and neurodegenerative conditions.

Brain sterol dysregulation in sporadic AD and MCI: relationship to heme oxygenase-1.

The objective of this study was to ascertain the impact of aging and Alzheimer's disease (AD) on brain cholesterol (CH), CH precursors, and oxysterol homeostasis. Altered CH metabolism and up-regulation of heme oxygenase-1 (HO-1) are characteristic of AD-affected neural tissues. We recently determined that HO-1 over-expression suppresses total CH levels by augmenting liver X receptor-mediated CH efflux and enhances oxysterol formation in cultured astroglia. Lipids and proteins were extracted from postmortem human frontal cortex derived from subjects with sporadic AD, mild cognitive impairment (MCI), and no cognitive impairment (n = 17 per group) enrolled in the Religious Orders Study, an ongoing clinical-pathologic study of aging and AD. ELISA was used to quantify human HO-1 protein expression from brain tissue and gas chromatography-mass spectrometry to quantify total CH, CH precursors, and relevant oxysterols. The relationships of sterol/oxysterol levels to HO-1 protein expression and clinical/demographic variables were determined by multivariable regression and non-parametric statistical analyses. Decreased CH, increased oxysterol and increased CH precursors concentrations in the cortex correlated significantly with HO-1 levels in MCI and AD, but not no cognitive impairment. Specific oxysterols correlated with disease state, increasing neuropathological burden, neuropsychological impairment, and age. A model featuring compensated and de-compensated states of altered sterol homeostasis in MCI and AD is presented based on the current data set and our earlier in vitro work.

Heme oxygenase-1 and neurodegeneration: expanding frontiers of engagement.

The heme oxygenases (HOs), responsible for the degradation of heme to biliverdin/bilirubin, free iron and CO, have been heavily implicated in mammalian CNS aging and disease. In normal brain, the expression of HO-2 is constitutive, abundant and fairly ubiquitous, whereas HO-1 mRNA and protein are confined to small populations of scattered neurons and neuroglia. In contradistinction to HO-2, the ho-1 gene (Hmox1) is exquisitely sensitive to induction by a wide range of pro-oxidant and other stressors. In Alzheimer disease and mild cognitive impairment, immunoreactive HO-1 protein is over-expressed in neurons and astrocytes of the cerebral cortex and hippocampus relative to age-matched, cognitively intact controls and co-localizes to senile plaques, neurofibrillary tangles, and corpora amylacea. In Parkinson disease, HO-1 is markedly over-expressed in astrocytes of the substantia nigra and decorates Lewy bodies in affected dopaminergic neurons. HMOX1 is also up-regulated in glial cells surrounding human cerebral infarcts, hemorrhages and contusions, within multiple sclerosis plaques, and in other degenerative and inflammatory human CNS disorders. Heme-derived free ferrous iron, CO, and biliverdin/bilirubin are biologically active substances that have been shown to either ameliorate or exacerbate neural injury contingent upon specific disease models employed, the intensity and duration of HO-1 expression and the nature of the prevailing redox microenvironment. In 'stressed' astroglia, HO-1 hyperactivity promotes mitochondrial sequestration of non-transferrin iron and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure amply documented in Alzheimer disease, Parkinson disease and other aging-related neurodegenerative disorders. Glial HO-1 expression may also impact cell survival and neuroplasticity in these conditions by modulating brain sterol metabolism and proteosomal degradation of neurotoxic protein aggregates.

Impact of heme oxygenase-1 on cholesterol synthesis, cholesterol efflux and oxysterol formation in cultured astroglia.

Up-regulation of heme oxygenase-1 (HO-1) and altered cholesterol (CH) metabolism are characteristic of Alzheimer-diseased neural tissues. The liver X receptor (LXR) is a molecular sensor of CH homeostasis. In the current study, we determined the effects of HO-1 over-expression and its byproducts iron (Fe(2+)), carbon monoxide (CO) and bilirubin on CH biosynthesis, CH efflux and oxysterol formation in cultured astroglia. HO-1/LXR interactions were also investigated in the context of CH efflux. hHO-1 over-expression for 3 days ( approximately 2-3-fold increase) resulted in a 30% increase in CH biosynthesis and a two-fold rise in CH efflux. Both effects were abrogated by the competitive HO inhibitor, tin mesoporphyrin. CO, released from administered CORM-3, significantly enhanced CH biosynthesis; a combination of CO and iron stimulated CH efflux. Free iron increased oxysterol formation three-fold. Co-treatment with LXR antagonists implicated LXR activation in the modulation of CH homeostasis by heme degradation products. In Alzheimer's disease and other neuropathological states, glial HO-1 induction may transduce ambient noxious stimuli (e.g. beta-amyloid) into altered patterns of glial CH homeostasis. As the latter may impact synaptic plasticity and neuronal repair, modulation of glial HO-1 expression (by pharmacological or other means) may confer neuroprotection in patients with degenerative brain disorders.