Pharmacotherapy for Spine-Related Pain in Older Adults.

As the population ages, spine-related pain is increasingly common in older adults. While medications play an important role in pain management, their use has limitations in geriatric patients due to reduced liver and renal function, comorbid medical problems, and polypharmacy. This review will assess the evidence basis for medications used for spine-related pain in older adults, with a focus on drug metabolism and adverse drug reactions. A PubMed/OVID search crossing common spine, neck, and back pain terms with key words for older adults and geriatrics was combined with common drug classes and common drug names and limited to clinical trials and age over 65 years. The results were then reviewed with identification of commonly used drugs and drug categories: nonsteroidal anti-inflammatories (NSAIDs), acetaminophen, corticosteroids, gabapentin and pregabalin, antispastic and antispasmodic muscle relaxants, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tramadol, and opioids. Collectively, 138 double-blind, placebo-controlled trials were the focus of the review. The review found a variable contribution of high-quality studies examining the efficacy of medications for spine pain primarily in the geriatric population. There was strong evidence for NSAID use with adjustments for gastrointestinal and renal risk factors. Gabapentin and pregabalin had mixed evidence for neuropathic pain. SNRIs had good evidence for neuropathic pain and a more favorable safety profile than TCAs. Tramadol had some evidence in older patients, but more so in persons aged < 65 years. Rational therapeutic choices based on geriatric spine pain diagnosis are helpful, such as NSAIDs and acetaminophen for arthritic and myofascial-based pain, gabapentinoids or duloxetine for neuropathic and radicular pain, antispastic agents for myofascial-based pain, and combination therapy for mixed etiologies. Tramadol can be well tolerated in older patients, but has risks of cognitive and classic opioid side effects. Otherwise, opioids are typically avoided in the treatment of spine-related pain in older adults due to their morbidity and mortality risk and are reserved for refractory severe pain. Whenever possible, beneficial geriatric spine pain pharmacotherapy should employ the lowest therapeutic doses with consideration of polypharmacy, potentially decreased renal and hepatic metabolism, and co-morbid medical disorders.

Acetaminophen (paracetamol) is safe in older adults, but non-steroidal anti-inflammatories (e.g. ibuprofen) may be more effective for spine-related pain. Non-steroidal anti-inflammatories should be used in short-term lower dose courses with gastrointestinal precaution. Corticosteroids have the least evidence for treating nonspecific back pain. Gabapentin and pregabalin may cause dizziness or difficulty walking, but may have some benefit for neck and back nerve pain (e.g. sciatica) in older adults. They should be used in lower doses with smaller dose adjustments. Some muscle relaxants (carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine) are avoided in older adults due to risk for sedation and falls. Others (tizanidine, baclofen, dantrolene) may be helpful for neck and back pain, with the most evidence for tizanidine and baclofen. These should be used in reduced doses, avoiding tizanidine with liver disease and reducing baclofen dosing with kidney disease. Older antidepressants are typically avoided in older adults due to their side effects, but nortriptyline and desipramine may be better tolerated for neck and back nerve pain at lower doses. Overall, newer antidepressants (namely duloxetine) have a better safety profile and good efficacy for spine-related nerve pain. Tramadol may be tolerated in older adults, but has risk for sedation, upset stomach, and constipation. It may be used in lower doses after alternative medications have failed, and works well with co-administered acetaminophen. Opioids are avoided due to their side effects and mortality risk, but low-dose opioid therapy may be helpful for severe refractory pain with close monitoring of patients clinically.

Cerebrospinal Fluid Removal for Idiopathic Intracranial Hypertension: Less Cerebrospinal Fluid Is Best.

BACKGROUND: Although lumbar punctures (LPs) are used for diagnostic evaluation in idiopathic intracranial hypertension (IIH), they can also provide relief from IIH-associated headache. Conversely, low-pressure headache secondary to LP can be debilitating. Low-volume cerebrospinal fluid (CSF) removal to a "high-normal" closing pressure (CP), approximately 18-20 cm H2O, may result in relief of IIH-associated headache with a lowered frequency of post-LP headache. METHODS: We conducted a single-center retrospective analysis from 2011 to 2016 of patients who underwent fluoroscopic LPs aiming for high-normal CPs. Inclusion criteria were as follows: 1) pre-existing diagnosis of IIH, or opening pressure (OP) and clinical findings diagnostic for IIH; 2) height and weight recorded within 1 year; 3) documented LP data parameters; and 4) one week post-LP follow-up documenting whether headache was worse, unchanged, or better. RESULTS: One hundred forty-six patients met the inclusion criteria. Mean age was 34.9 years ± 11.0, and mean body mass index was 39.2 kg/m ± 10.5. Mean volume removed was 9.7 mL ± 4.6. The mean CP was 17.9 cm H2O ±2.7. The mean pressure change (OP-CP) per volume removed was 1.50 cm H2O/mL ±0.6. Headache symptoms at follow-up were improved in 64% (80/125) of patients, worse in 26% (33/125), and unchanged in 10% (12/125). Eleven patients were headache-free, and 11 patients required hospital care for post-LP headache. CONCLUSIONS: Low-volume CSF removal to approximately 18 cm H2O resulted in relief of IIH-associated headache in most patients and a low incidence of post-LP headache. Although clinically variable, these data suggest that for every 1 mL of CSF removed, the CP decreases approximately 1.5 cm H2O.

Radicular Pain Syndromes: Cervical, Lumbar, and Spinal Stenosis.

Back pain is a top primary and urgent care complaint; radicular pain can be caused by herniation of the nucleus pulposus (intervertebral disc), spinal stenosis, or degenerative changes to the vertebrae. The focus of this clinical review will be the clinical approach and treatment of lumbar radicular pain, cervical radicular pain, and spinal stenosis. Usually localized through neurological history, exam, and imaging, specific signs and symptoms for lumbar radicular, spinal stenosis, and cervical radicular pain can help determine etiology. Once radicular back pain has been diagnosed, a multitude of treatment options are available from rest and physical therapy to medications, epidurals, and surgery. The most common and accepted are reviewed. With accurate diagnosis, safe and effective pain management can be employed to shorten radicular episodes and manage recurrent or chronic radicular syndromes. Using a step-wise approach from diagnosis to conservative therapy to potential surgery, radicular pain syndromes can improve or resolve, and patients may achieve a better functional status and quality of life.

Cerebellar stroke presenting with isolated dizziness: Brain MRI in 136 patients.

OBJECTIVE: To evaluate occurrence of cerebellar stroke in Emergency Department (ED) presentations of isolated dizziness (dizziness with a normal exam and negative neurological review of systems). METHODS: A 5-year retrospective study of ED patients presenting with a chief complaint of "dizziness or vertigo", without other symptoms or signs in narrative history or on exam to suggest a central nervous system lesion, and work-up included a brain MRI within 48h. Patients with symptoms commonly peripheral in etiology (nystagmus, tinnitus, gait instability, etc.) were included in the study. Patient demographics, stroke risk factors, and gait assessments were recorded. RESULTS: One hundred and thirty-six patients, who had a brain MRI for isolated dizziness, were included. There was a low correlation of gait assessment between ED physician and Neurologist (49 patients, Spearman's correlation r2=0.17). Based on MRI DWI sequence, 3.7% (5/136 patients) had acute cerebellar strokes, limited to or including, the medial posterior inferior cerebellar artery vascular territory. In the 5 cerebellar stroke patients, mean age, body mass index (BMI), hemoglobin A1c, gender distribution, and prevalence of hypertension were similar to the non-cerebellar stroke patient group. Mean LDL/HDL ratio was 3.63±0.80 and smoking prevalence was 80% in the cerebellar stroke group compared to 2.43±0.79 and 22% (respectively, p values<0.01) in the non-cerebellar stroke group. CONCLUSIONS: Though there was preselection bias for stroke risk factors, our study suggests an important proportion of cerebellar stroke among ED patients with isolated dizziness, considering how common this complaint is.

Practical considerations in opioid use for brain neoplasm.

Neurologists are often on the front lines of diagnosis for primary and metastatic brain tumors. Patients with brain tumors typically have multiple comorbidities and pain generators beyond headache, necessitating opioid therapy. Opioid-based pain relief and safety in the medically ill patient are complex. While using the lowest-potency opioid with adjunct medications is always prudent, patients with brain tumors frequently require dose escalation. Opioid selection and use is based on the patient's respiratory and cardiac function as well as drug clearance capability. Specific opioid combinations, employing long-acting and short-acting drugs, have greater efficacy in specific patient profiles and make adverse drug reactions, toxicity, abuse, and diversion less likely.

Beyond neuropathic pain: gabapentin use in cancer pain and perioperative pain.

BACKGROUND: Gabapentin (GBP), originally an antiepileptic drug, is more commonly used in the treatment of neuropathic pain. In recent years, GBP has been used as an adjunct or primary therapy in non-neuropathic pain, most commonly for the treatment of perioperative and cancer pain. OBJECTIVES: The aim of this study was to conduct a clinical evidence literature review of GBP's use in perioperative pain and cancer pain. METHODS: Using PUBMED and OVID Medline databases, keyword searches for surgery and cancer in reference to GBP and pain were carried out. Nonblinded studies and case reports that did not present a unique finding were excluded. Studies that focused only on neuropathic pain were also excluded. RESULTS: An initial 142 references focusing on GBP's use in surgical pain and cancer pain were identified. Of these, 48 studies were quality of evidence at a level of II-2 or higher. DISCUSSION: Although efficacy varies, multiple well-designed clinical trials have demonstrated reduced pain and analgesic use with otolaryngology, orthopedic, mastectomy, and abdominal/pelvic surgical perioperative use of GBP, whereas there is limited or no efficacy for cardiothoracic surgery. Cancer pain studies have had greater design variability, often nonblinded, with pain benefit being mild to moderate, and more efficacious with partial neuropathic pain quality. Overall, GBP seems to have significant benefit in neuropathic and non-neuropathic pain associated with the perioperative period and cancer. Considering its favorable side effect profile, GBP represents a beneficial pain adjunctive therapy, beyond neuropathic symptoms.

Differential modulation of P-glycoprotein expression and activity by non-nucleoside HIV-1 reverse transcriptase inhibitors in cell culture.

PURPOSE: This study investigated the effects of the non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTI) nevirapine (NVR), efavirenz (EFV), and delavirdine (DLV) on P-glycoprotein (P-gp) activity and expression to anticipate P-gp related drug-drug interactions associated with combination therapy. METHODS: NNRTIs were evaluated as P-gp substrates by measuring differential transport across Caco-2 cell monolayers. Inhibition of P-gp mediated rhodaminel23 (Rh123) transport in Caco-2 cells was used to assess P-gp inhibition by NNRTIs. Induction of P-gp expression and activity in LS180V cells following 3-day exposure to NNRTIs was measured by western blot analysis and cellular Rh123 uptake, respectively. RESULTS: The NNRTIs showed no differential transport between the basolateral to apical and apical to basolateral direction. NNRTI transport in either direction was not affected by the P-gp inhibitor verapamil. DLV inhibited Rh123 transport, causing a reduction to 15% of control at 100 microM (IC50 = 30 microM). NVR caused a concentration-dependent induction of P-gp expression in LS180V cells resulting in a 3.5-fold increase in immunoreactive P-gp at 100 microM NVR. Induction attributable to EFV and DLV was quantitatively smaller. NVR significantly reduced cellular uptake of Rh123 into LS180V cells, indicating increased drug efflux due to induced P-gp activity; effects of EFV and DLV were smaller. Acute DLV treatment of LS180V cells previously induced with NVR or ritonavir did not reverse the decreased Rh123 cell accumulation. CONCLUSIONS: NNRTIs show differential effects on P-gp activity and expression in vitro. Clinical studies are required to elucidate the clinical importance of potential drug interactions.