Current Strategies for the Management of Painful Diabetic Neuropathy.

The development of painful diabetic neuropathy (PDN) is a common complication of chronic diabetes that can be associated with significant disability and healthcare costs. Prompt symptom identification and aggressive glycemic control is essential in controlling the development of neuropathic complications; however, adequate pain relief remains challenging and there are considerable unmet needs in this patient population. Although guidelines have been established regarding the pharmacological management of PDN, pain control is inadequate or refractory in a high proportion of patients. Pharmacotherapy with anticonvulsants (pregabalin, gabapentin) and antidepressants (duloxetine) are common first-line agents. The use of oral opioids is associated with considerable morbidity and mortality and can also lead to opioid-induced hyperalgesia. Their use is therefore discouraged. There is an emerging role for neuromodulation treatment modalities including intrathecal drug delivery, spinal cord stimulation, and dorsal root ganglion stimulation. Furthermore, consideration of holistic alternative therapies such as yoga and acupuncture may augment a multidisciplinary treatment approach. This aim of this review is to focus on the current management strategies for the treatment of PDN, with a discussion of treatment rationale and practical considerations for their implementation.

Patients with chronic pain and dysphagia (CPD): unmet medical needs and pharmacologic treatment options.

BACKGROUND: For properly selected patients experiencing chronic pain, extended-release opioid formulations may represent an appropriate pain management choice. For the many adults, elderly, and children who have medical conditions that make swallowing solid, oral-dose formulations difficult (dysphagia) or painful (odynophagia), this option may be limited. The combination of chronic pain with dysphagia (CPD) presents a challenge to physicians and patients alike when oral opioid analgesia is needed to control pain, but patients are unable to swallow solid, oral dosage forms. METHODS: A Medline search was performed (1990 to 2013) using the search terms swallowing difficulties, dysphagia, odynophagia, adults, pediatrics, elderly, chronic pain, pain, and opioids. The following websites were searched: American Dysphagia Network, Dysphagia Research Society, World Health Organization, American Pain Society, International Association for the Study of Pain, American Academy of Pain Medicine, and American Society of Interventional Pain Physicians. Chronic pain guidelines from the following professional organizations were searched: American Pain Society, National Comprehensive Cancer Network, American Society of Interventional Pain Physicians, British Geriatric Society, European Society of Medical Oncology, World Health Organization, and the European Association for Palliative Care. FINDINGS: There is an unmet medical need for greater recognition of dysphagia, awareness of potential problems with medication administration in these patients, recognition of alternative drug formulations that are available for use in CPD, and an appreciation that there are new, solid, oral-dose, opioid formulations in development that can mitigate these issues associated with swallowing difficulty while still providing practical, effective analgesia. Current pharmacologic treatments have limitations; new, prospective opioid formulations in clinical development may offer physicians and patients with CPD effective treatment options while mitigating accidental exposure and abuse liability. CONCLUSIONS: The number of patients with CPD may be larger than is currently anticipated by healthcare providers. Physicians should proactively include a discussion of dysphagia as part of the patient examination. CPD is an unmet medical need. There are novel opioid formulations in clinical development that address the limitations of current opioid treatments. This manuscript reviews the problems associated with dysphagia on medication administration and adherence, currently available treatment options, and opioid analgesic formulations currently in clinical development.

Evidence-based guidance for the management of postherpetic neuralgia in primary care.

This article aims to help primary care physicians negotiate gaps in current guidelines for postherpetic neuralgia (PHN). The objectives of this article are to: 1) briefly review the available guidelines and identify their strengths and weaknesses; 2) review the gaps in the guidelines; 3) review new data that were not included in the most recent guidelines; 4) provide expert opinion on how the new data and current guidelines can be used to make treatment decisions; and 5) review several important dimensions of care (eg, tolerability, dosing) and provide guidance. In general, all guidelines recognize the α2δ ligands, tricyclic antidepressants (TCAs), opioids, and tramadol as efficacious systemic options, with topical lidocaine serving as an efficacious nonsystemic approach for localized PHN treatment. The first-line treatment options typically recommended in the guidelines are α2δ ligands and TCAs, while opioids and tramadol are often recommended as second- or third-line options. Since the latest guidelines were published, newer agents (eg, topical capsaicin [8%] patch and gastroretentive gabapentin) have met the standard as first-line therapy with the publication of ≥ 1 randomized controlled trial. However, gabapentin enacarbil has not met this standard due to a lack of a published randomized controlled trial in PHN.

Review of current guidelines on the care of postherpetic neuralgia.

An unfortunate minority of patients with acute herpes zoster (AHZ) experience pain beyond the typical 4-week duration, and roughly 10% develop the distressing complication of postherpetic neuralgia (PHN), often defined as pain persisting for > 4 months after the onset of the rash. Elderly patients are at increased risk of PHN. The pathophysiology of PHN is complex, likely involving both peripheral and central processes. This complexity may create opportunities for pharmacologic interventions with multiple differing mechanisms of action. Consequently, complementary combinations of pharmacologic agents are frequently more effective than any monotherapy. Current US and international guidelines on the care of patients with PHN are reviewed and interpreted here to facilitate their effective incorporation into the practice of primary care physicians, acknowledging the contrasts that often exist between the clinical trial populations analyzed to craft so-called evidence-based medicine and the individual patients seen in daily practice, many of whom may not have been candidates for those clinical trials. First-line treatments for PHN include tricyclic antidepressants, gabapentin and pregabalin, and the topical lidocaine 5% patch. Opioids, tramadol, capsaicin cream, and the capsaicin 8% patch are recommended as either second- or third-line therapies in different guidelines. Therapies that have demonstrated effectiveness for other types of neuropathic pain are discussed, such as serotonin-norepinephrine reuptake inhibitors, the anticonvulsants carbamazepine and valproic acid, and botulinum toxin. Invasive procedures such as sympathetic blockade, intrathecal steroids, and implantable spinal cord stimulators have been studied for relief of PHN, mainly in patients refractory to noninvasive pharmacologic interventions. The main guidelines considered here are those issued by the American Academy of Neurology for the treatment of postherpetic neuralgia (2004) and general guidelines for the treatment of neuropathic pain issued by the Special Interest Group on Neuropathic Pain of the International Association for the Study of Pain (2007) and the European Federation of Neurological Societies (2010).

Topical agents for the treatment of chronic pain.

Unlike systemic analgesics, topical analgesics exert their analgesic activity locally and without significant systemic absorption. This is in contrast to transdermal analgesics, which require systemic absorption for clinical benefit. The mechanism of action of a particular topical analgesic is unique to the specific medication being used as a topical analgesic. Topical analgesics have been studied in an increasing number of painful clinical conditions, and the results of some of these studies are summarized in this article. The potential role of topical analgesics acting peripherally in affecting the central processing of pain as well as painful states considered to be "central," not "peripheral," also are reviewed.

Treatment of postherpetic neuralgia: a review of therapeutic options.

Postherpetic neuralgia (PHN) is a disabling consequence of the reactivation of the varicella zoster infection. The observation that patients with PHN experience various types of pain suggests that multiple pathophysiologic mechanisms are involved, which may include the peripheral and central nervous systems. A reasonable initial strategy would involve selecting from among multiple agents that have complementary mechanisms of action and that have been proven effective in controlled clinical trials, such as the lidocaine patch 5%, gabapentin, tricyclic antidepressants, and opioids. Based on initial assessment and ongoing reassessment, sequential trials should be undertaken until adequate pain relief is achieved. This may ultimately lead to therapy with more than one medication. Safety and tolerability are important considerations in choosing initial therapy, particularly in older patients. Physicians can either add another agent to the current regimen or switch to a new type of monotherapy if there is inadequate response to initial therapy. Alternative therapies, (i.e., ketamine, intrathecal corticosteroid injections) have not been adequately studied. Well-designed, multicenter, controlled clinical trials are needed to develop a treatment algorithm that provides an evidence-based, rational approach to treating PHN.

A review of the use of topical analgesics for myofascial pain.

Numerous treatment strategies for myofascial pain syndrome are available, including physical therapy, behavioral pain management techniques, acupuncture, various types of injections, and the use of various pharmacotherapeutic approaches. The use of topical analgesics for myofascial pain syndrome is the focus of this review. The use of topical analgesics in other painful states is also reviewed.

A focused review on the use of botulinum toxins for neuropathic pain.

Understanding the pathophysiology of a pain syndrome is helpful in selecting appropriate treatment strategies. Nociceptive pain is related to damage to tissues due to thermal, chemical, mechanical, or other types of irritants. Neuropathic pain results from injury to the peripheral or central nervous system. Common examples of neuropathic pain include postherpetic neuralgia, diabetic neuropathy, complex regional pain syndrome, and pain associated with spinal cord injuries. Nociceptive pain may have similar clinical characteristics to neuropathic pain. It is also possible for acute nociceptive pain to become neuropathic in nature, as with myofascial pain syndrome. A clear benefit of botulinum toxin therapy for treatment of neuropathic pain disorders is that it often relieves pain symptoms. Although the precise mechanism of pain relief is not completely understood, the injection of botulinum toxin may reduce various substances that sensitize nociceptors. As a result, botulinum toxin types A and B are now being actively studied in nociceptive and neuropathic pain disorders to better define their roles as analgesics.