The Role of Genetic Polymorphisms in Chronic Pain Patients.

It is estimated that the total annual financial cost for pain management in the U.S. exceeds 100 billion dollars. However, when indirect costs are included, such as functional disability and reduction in working hours, the cost can reach more than 300 billion dollars. In chronic pain patients, the role of pharmacogenetics is determined by genetic effects on various pain types, as well as the genetic effect on drug safety and efficacy. In this review article, we discuss genetic polymorphisms present in different types of chronic pain, such as fibromyalgia, low back pain, migraine, painful peripheral diabetic neuropathy and trigeminal neuralgia. Furthermore, we discuss the role of CYP450 enzymes involved in metabolism of drugs, which have been used for treatment of chronic pain (amitriptyline, duloxetine, opioids, etc.). We also discuss how pharmacogenetics can be applied towards improving drug efficacy, shortening the time required to achieve therapeutic outcomes, reducing risks of side effects, and reducing medical costs and reliance upon polypharmacy.

Lumbar epidural analgesia for labor in a parturient with a history of surgery for lumbar intradural ependymoma: Literature review and case presentation.

BACKGROUND: Ependymomas represent 50-60% of all brain and central nervous system tumors. Previous lumbar spine surgery for resection of an ependymoma should not be considered a relative contraindication for the administration of epidural/subarachnoid anesthesia to patients in labor. CASE DESCRIPTION: A 34-year-old G1P0, who underwent resection of an L1-L3 intramedullary ependymoma 8 years previously, presented in active labor with residual left leg numbness and tingling. The lumbar magnetic resonance imaging showed scar tissue and the L1-L3 laminectomy defect. With the acute onset of labor pain, the patient underwent continuous lumbar epidural analgesia; the epidural catheter was placed at the L5-S1 level. The patient underwent an emergency cesarean section with surgical anesthesia being attained up to a T4 dermatomal sensory level. CONCLUSIONS: Neuraxial anesthesia can be performed safely in patients who have previously undergone lumbar resections of intradural ependymomas. However, the anesthesiologist should place the epidural needle/catheter at a nonoperative level (e.g. above/below). Furthermore, epidural local anesthetics and opioids, as in this case, placed at the L5-S1 level below an L1-L3 prior surgical scar, may diffuse intradurally, bypassing the obliterated surgical epidural space and/or attendant scar tissue.

Management of parturients in active labor with Arnold Chiari malformation, tonsillar herniation, and syringomyelia.

BACKGROUND: Arnold-Chiari malformation Type 1 (ACM-1) in parturients is a topic of ongoing discussion between obstetricians and anesthesiologists. The primary unanswered question remains; How should the anesthesia provider proceed with labor analgesia and anesthesia for cesarean section when confronted with an advanced, asymptomatic, or minimally symptomatic case of ACM-1 during labor? CASE DESCRIPTION: A 24-year-old, ASA II, G1P0 full-term parturient presented to Labor and Delivery for vaginal delivery. A diagnosis of ACM-1 was made 12 years ago when a brain magnetic resonance imaging (MRI) was performed for right-sided numbness following a rear-end motor vehicle collision. The patient had been asymptomatic since then and had been seen by an outside neurologist frequently for the past 10 years. During the anesthesia evaluation, it was noted that she had an exaggerated patellar reflex, and a questionable left-sided Babinski; subsequently, an MRI study was requested. Review of a brain MRI demonstrated an advanced form of ACM with a 1.7 cm transtonsillar herniation and a large syrinx extending from C1 down to C5. Following a discussion with the patient, family, and primary OB team, a plan for elective cesarean section was made per neurosurgical recommendations. This was conducted uneventfully under general anesthesia. The patient had no complaints in the post-anesthesia care unit. CONCLUSION: Unfamiliarity of health care providers with regards to ACM-1 parturients can be countered by increasing awareness of this condition throughout medical specialties involved in their care. The Ghaly Obstetric Guide to Arnold-Chiari malformation Type 1, along with proper training of anesthesia care providers regarding the specificities of ACM-1 parturients aids in better management and understanding of this complex condition.

Management of chronic neuropathic pain with single and compounded topical analgesics.

The goal of our review was to emphasize important aspects that physicians should take into consideration when prescribing topical analgesics as part of chronic neuropathic pain treatment. We discuss the dermatopharmacokinetics and microstructural components of the skin, differences between topical and transdermal drug delivery, and topical medication effects on peripheral neuropathy and central sensitization. Even though the US FDA approved topical analgesics are 8%-capsaicin and 5%-lidocaine patches for treating postherpetic neuralgia, there are many other studies conducted on the efficacy of topical ketamine cream, clonidine gel, topical gabapentin, topical baclofen and topical phenytoin for peripheral neuropathic pain, either alone or in combination with other formulations. Furthermore, we discuss new compounded topical analgesics that are becoming more popular and that are showing promising results in the management of chronic peripheral neuropathies. However, more studies are needed for elucidation of the role of topical analgesics and their effects, especially when combined with other treatments.

Do we need to establish guidelines for patients with neuromodulation implantable devices, including spinal cord stimulators undergoing nonspinal surgeries?

BACKGROUND: Spinal cord stimulation is currently approved to treat chronic intractable pain of the trunk and limbs. However, such implantable electronic devices are vulnerable to external electrical currents and magnetic fields. Within the hospitals and modern operating rooms (ORs), there is an abundance of electrical devices and other types of equipment that could interfere with such devices. Despite the increasing number of patients with neuromodulation implantable devices, there are no written guidelines available or consensus of cautions for such patients undergoing unrelated surgery. CASE DESCRIPTIONS: A 60-year-old female with a permanent St. Jude's spinal cord stimulator (SCS) presented for open total abdominal hysterectomy. Both the anesthesia and gynecology staffs were aware of the device presence, but were unaware of any precautions regarding intraoperative management. The device was found to be nonmagnetic resonance imaging compatible, and bipolar cautery was used instead of monopolar cautery. A 59-year-old female with a 9-year-old permanent Medtronic SCS, presented for right total hip arthroplasty. The device was switched off prior to entering the OR, bipolar cautery was used, and grounding pads were placed away from her battery site. In each case, the manufacturer's representative was contacted preoperative. Both surgeries proceeded uneventfully. CONCLUSIONS: The Food and Drug Administration safety information manual warns about the use of diathermy, concomitant implanted stimulation devices, lithotripsy, external defibrillation, radiation therapy, ultrasonic scanning, and high-output ultrasound, all of which can lead to permanent implant damage if not turned off prior to undertaking procedures. Lack of uniform guidelines makes intraoperative management, as well as remote anesthesia care of patients with previously implanted SCSs unsafe.

The role of cytochrome P450 pharmacogenomics in chronic non-cancer pain patients.

INTRODUCTION: Pharmacogenomics is the field that studies an individualized treatment approach for patients' medication regimen that can impact drug safety, productivity, and personalized health care. Pharmacogenomics characterizes the genetic differences in metabolic pathways which can affect a patient's individual responses to drug treatments. Areas covered: The various responses to pharmacological agents are mainly determined by the different types of genetic variants of the CYP450. CYP2D6 polymorphism is well known for its variation in the metabolism of drugs from many therapeutic arenas, including some analgesic drugs such as codeine, hydromorphone, oxycodone and tramadol. Allele combinations determine the phenotypic expression, characterized as either: extensive metabolizer, intermediate metabolizer, ultra-rapid metabolizer and poor metabolizer. Expert opinion: The Human Genome Project (HGP) revolutionized the future of medicine and the way health care providers approach individualized patient treatment, and chronic pain management is one of those areas. The key findings in the literature appear to be related to the CYP2D6 expression and its high polymorphism influencing the metabolism of opioid medications, and the impact of that on the patient's therapeutic outcome thus exemplifying the importance of genetic testing for CYP2D6 in the process of physician therapeutic decision making.

Spinal neuromodulation as a novel surgical option for failed back surgery syndrome following rhBMP exuberant bony growth in instrumented lumbar fusion: A case report and literature review.

BACKGROUND: Bone morphogenic protein (BMP) for instrumented lumbar fusion was approved in 2002, and since then has led to an increasing incidence of BMP-related neuropathic pain. These patients are usually resistant to conventional medical therapy and frequently undergo multiple surgical revisions without any pain relief. CASE DESCRIPTION: A 58-year-old male was referred to the author's outpatient clinic after four lumbar surgeries did not provide satisfactory pain relief. During his 10 years of suffering from low back pain after an injury, the patient was resistant to conventional and interventional treatment options. He was experiencing severe back pain rated 10/10, as well as right lower extremity pain, numbness, tingling, and motor deficits. Outside spine specialists had performed revision surgeries for BMP-related exuberant bone formation at L5-S1, which included the removal of the ipsilateral hardware and debridement of intradiscal and intraforamina heterotrophic exuberant bony formation. The author implanted the patient with a permanent continuous spinal cord stimulator, after which he achieved complete pain relief (0/10) and restoration of motor, sensory, autonomic, and sphincter functions. CONCLUSION: This is the first reported case of restorative function with neuromodulation therapy in a BMP-induced postoperative complication, which is considered as a primarily inflammatory process, rather than nerve root compression due to exuberant bony formation. We hypothesize that neuromodulation may enhance blood flow and interfere with inflammatory processes, in addition to functioning by the accepted gate control theory mechanism. The neuromodulation therapy should be strongly considered as a therapeutic approach, even with confirmed BMP-induced postoperative radiculitis, rather than proposing multiple surgical revisions.

Unique pharmacology of tapentadol for treating acute and chronic pain.

INTRODUCTION: Even though pain is a complex process involving many different mediators, enzymes, receptors and ion channels, pain medications usually address only individual targets. Nucynta, which addresses multiple pain targets, was the first new centrally acting analgesic to be approved by the FDA in 2008. AREAS COVERED: Pharmacology: Tapentadol is a centrally acting opioid with two mechanisms of action, including agonism at the µ-opioid receptor (MOR) and inhibition of norepinephrine reuptake (NRI), producing analgesia individually and via a combination of both acts synergistically at the spinal and supraspinal levels. The pharmacokinetics of both forms of tapentadol (immediate release-IR and extended release-ER) is relatively predictable and stable in healthy individuals. Clinical efficacy: Tapentadol IR was studied in clinical trials involving patients mainly with postoperative pain, but also in patients suffering from acute low back pain and osteoarthritis-related pain. Tapentadol ER was approved for management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. EXPERT OPINION: Although future improved, well-designed prospective, randomized double-blind controlled studies are needed to determine both the relative efficacy of tapentadol and its safety, we believe that tapentadol has the potential to become a uniquely suited opioid medication in the multi-modal management of moderate-to-severe acute and chronic pain conditions.