Pregabalin Vs. Opioids for the Treatment of Neuropathic Cancer Pain: A Prospective,Head‐to‐Head,Randomized, Open‐Label Study

Objectives

Neuropathic cancer pain (NCP) is a common manifestation of cancer and/or its treatment. Treatment following the WHO analgesic ladder provides relief for the majority of cancer pain patients; however, concern remains that opioids may be less efficacious for neuropathic pain (NP) compared with nociceptive pain, often necessitating the use of higher doses. Adjuvants, such as pregabalin, have shown to be efficacious for the treatment of NP, although data come mostly from noncancer studies. The comparative efficacy and safety of opioids versus adjuvants has not been studied for NCP. The aim of this study was to directly compare pregabalin versus a strong opioid for the treatment of NCP.

Methods

A total of 120 patients, diagnosed with “definite” NCP, were randomized into two groups and received increasing doses of either oral pregabalin or transdermal fentanyl for 28 days. VAS score, patient satisfaction, need for opioid rescue, and adverse events (AEs) were recorded.

Results

In the pregabalin group, a significantly higher proportion of patients achieved at least 30% reduction in VAS compared with the fentanyl group (73.3%, 95% CI: 60.3%–83.93 vs. 36.7%, 95% CI: 24.5%–50.1%, P < 0.0001, respectively), while the percentage mean change from baseline was also significantly different [46% (95% CI: 39.5%–52.8%) for pregabalin and 22% (95% CI: 14.9%–29.5%) for fentanyl (P < 0.0001)]. Patient‐reported satisfaction was more frequent with pregabalin, while AEs and treatment discontinuations were more frequent in the fentanyl group.

Discussion

Prompt use of a neuropathic pain‐specific adjuvant, such as pregabalin, in NCP may lead to better control of the neuropathic component, with opioid‐sparing effects.     

A Review of Duloxetine 60 mg Once‐Daily Dosing for the Management of Diabetic Peripheral Neuropathic Pain,Fibromyalgia, and Chronic Musculoskeletal Pain Due to Chronic Osteoarthritis Pain and Low Back Pain

Background: Duloxetine is a selective dual neuronal serotonin (5‐Hydroxytryptamine, 5‐HT) and norepinephrine reuptake inhibitor (SSNRI). It is indicated in the United States for treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and several chronic pain conditions, including management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic osteoarthritis (OA) pain and chronic low back pain (LBP). Its use for antidepressant and anxiolytic actions has been extensively reviewed previously. We here review the evidence for the efficacy of 60 mg once‐daily dosing of duloxetine for chronic pain conditions. Method: The literature was searched for clinical trials in humans conducted in the past 10 years involving duloxetine. Results: There were 199 results in the initial search. Studies not in the English language were excluded. We then included only studies of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain (OA and LBP). Studies of painful symptoms reported in mental health studies were excluded. This resulted in 32 studies. Articles that did not include a 60 mg/day daily dose as a study arm were excluded. This resulted in 30 studies, broken down as follows: 12 for diabetic peripheral neuropathy, 9 for fibromyalgia, 6 for LBP, and 3 for OA pain. Conclusions: The studies reviewed report that duloxetine 60 mg once‐daily dosing is an effective option for the management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic OA pain and chronic LBP. As these pains are often comorbid with MDD or GAD, duloxetine might possess the pharmacologic properties to be a versatile agent able to address several symptoms in these patients. With adequate attention to FDA prescribing guidance regarding safety and drug–drug interactions, duloxetine 60 mg once‐daily dosing appears to be an effective option in the appropriate pain patient population.     

Pain Management in Four‐Limb Amputation: A Case Report

Acute pain following amputation can be challenging to treat due to multiple underlying mechanisms and variable clinical responses to treatment. Furthermore, poorly controlled preoperative pain is a risk factor for developing chronic pain. Evidence suggests that epidural analgesia and peripheral nerve blockade may decrease the severity of residual limb pain and the prevalence of phantom pain after lower extremity amputation. We present the perioperative analgesic management of a patient with gangrene of the bilateral upper and lower extremities as a result of septic shock and prolonged vasopressor administration who underwent four‐limb amputation in a single procedure. A multimodal analgesic regimen was utilized, including titration of preoperative opioid and neuropathic pain agents, perioperative intravenous, epidural and peripheral nerve catheter infusions, and postoperative oral medication titration. More than 8 months postoperatively, the patient has satisfactory pain control with no evidence for phantom limb pain. To our knowledge, there have been no publications to date concerning analgesic regimens in four‐limb amputation.     

An Open‐Label Comparison of Nabilone and Gabapentin as Adjuvant Therapy or Monotherapy in the Management of Neuropathic Pain in Patients with Peripheral Neuropathy

Neuropathic pain (NeP) is prevalent in patients with peripheral neuropathy (PN), regardless of etiology. We sought to compare the efficacy of the cannabinoid nabilone as either monotherapy or adjuvant therapy with a first‐line medication for NeP, gabapentin, in a patient population with PN‐NeP. Patients diagnosed with PN‐NeP were permitted to initiate monotherapy (nabilone or gabapentin) or add one of these two medications (adjuvant therapy) to their existing NeP treatment regimen in a non‐randomized open‐label nature. Baseline data collected included a primary outcome (visual analog scores [VAS] of pain) and secondary outcomes (quality of life [EuroQol 5 Domains and Short‐Form 36] assessments and assessments of sleep [Medical Outcomes Sleep Study Scale {MOSSS}], anxiety and depression [Hospital Anxiety and Depression Scale], and pain [Brief Pain Inventory]). Reassessment and modulation of dosing and/or medications occurred at 3‐ and 6‐month intervals. Medication adverse effects and drug efficacy, as well as questionnaires, were assessed at 6 months. Matched analysis of variance testing was performed to compare 3‐ and 6‐month scores with baseline, as well as to compare therapies at equal time points. Significant improvements in pain VAS were seen in all treatment groups at 6 months. Numerous sleep parameters within MOSSS, Brief Pain Inventory, and Short‐Form 36 improved in patients receiving nabilone or gabapentin either as monotherapy or adjuvant treatment. Hospital Anxiety and Depression Scale‐A scores were significantly improved in all treatment groups. Sleep adequacy and the sleep problems index within the MOSSS improved in nabilone monotherapy patients in particular. The benefits of monotherapy or adjuvant therapy with nabilone appear comparable to gabapentin for management of NeP. We advocate for head‐to‐head randomized, double‐blind studies for current therapies for NeP in order to determine potential advantages beneficial in this patient population.     

Long‐Term Response of Neuropathic Pain to Intravenous Immunoglobulin in Relapsing Diabetic Lumbosacral Radiculoplexus Neuropathy. A Case Report

Diabetic lumbosacral radiculoplexus neuropathy (DLRPN) is a rare painful peripheral neuropathic complication of diabetes mellitus. The clinical features of DLRPN include severe neuropathic pain, weakness, atrophy, and sensory loss in the lower limbs with asymmetrical distribution. Nerve ischemia due to inflammation and microvasculitis has been suggested as the pathophysiological mechanism for DLRPN. Analgesics and drugs for neuropathic pain often cannot achieve adequate pain control in DLRPN. Some reports suggest that intravenous immunoglobulin (IVIg) may reduce pain in DLRPN, but the mechanisms of this effect are unclear. We report a patient with relapsing DLRPN who was followed up for 8 years and whose pain improved after IVIg on nine occasions. We measured serum cytokines before and after IVIg; serum tumor necrosis factor α was increased when the patient reported pain and normalized after IVIg in parallel with pain improvement. Our data extend the notion that some types of pain, including peripheral neuropathic pain, may respond to IVIg and give some clue on the mechanism of this therapeutic effect. They are also consistent with the suggested role of the immune system in the pathophysiology of neuropathic pain and offer support to the hypothesis that cytokines may contribute to the pathogenesis of neuropathic pain.