Can Chronic Pain Patients Be Adequately Treated Using Generic Pain Medications to the Exclusion of Brand-Name Ones?

According to the Food and Drug Administration (FDA) reports, approximately 8 in 10 prescriptions filled in the United States are for generic medications, with an expectation that this number will increase over the next few years. The impetus for this emphasis on generics is the cost disparity between them and brand-name products. The use of FDA-approved generic drugs saved 158 billion dollars in 2010 alone. In the current health care climate, there is continually increasing pressure for prescribers to write for generic alternative medications, occasionally at the expense of best clinical practices. This creates a conflict wherein both physicians and patients may find brand-name medications clinically superior but nevertheless choose generic ones. The issue of generic versus brand medications is a key component of the discussion of health payers, physicians and their patients. This review evaluates some of the important medications in the armamentarium of pain physicians that are frequently used in the management of chronic pain, and that are currently at the forefront of this issue, including Opana (oxymorphone; Endo Pharmaceuticals, Inc., Malvern, PA), Gralise (gabapentin; Depomed, Newark, CA), and Horizant (gabapentin enacarbil; XenoPort, Santa Clara, CA) that are each available in generic forms as well. We also discuss the use of Lyrica (pregabalin; Pfizer, New York, NY), which is currently unavailable as generic medication, and Cymbalta (duloxetine; Eli Lilly, Indianapolis, IN), which has been recently FDA approved to be available in a generic form. It is clear that the use of generic medications results in large financial savings for the cost of prescriptions on a national scale. However, cost-analysis is only part of the equation when treating chronic pain patients and undervalues the relationships of enhanced compliance due to single-daily dosing and stable and reliable pharmacokinetics associated with extended-duration preparations using either retentive technologies or delayed absorption strategies. Medications given to chronic pain patients should be individualized to best serve analgesic needs and assure patient safety primarily, based on high levels of scientific and economic evidence. Decisions regarding utilization should not be made based solely on limited or faulty assessments of cost-benefit analyses.

Transcriptome analysis of mammary tissues reveals complex patterns of transporter gene expression during pregnancy and lactation.

As a complex Ca2+-rich fluid mixture of water, casein, lactose and several ions, milk secretion requires a number of unknown transporters, which can be identified by a genome-wide microarray study in mammary tissues of lactating animals. Ca2+ was reported to be secreted across mammary epithelial cells through the transcellular pathway, presumably involving TRPC (canonical transient receptor potential) channels. In the present study, we have used quantitative real-time PCR to demonstrate that the human mammary cell line MCF-7, as well as rat mammary tissues from pregnant and lactating rats, expressed TRPC1, TRPC5 and TRPC6. Expression of TRPC1, TRPC5 and TRPC7 were markedly up-regulated, whereas that of TRPC3 and TRPC4 was down-regulated in the early lactating period. To further identify other transporter genes affected by lactation, a highly sensitive Illumina microarray featuring Bead Array technology was performed on RNA samples from mammary tissues of lactating rats. We found that, of the 384 transcripts changed during lactation, 31 transcripts were involved in the transport of water and electrolytes, such as Ca2+, Na+, K+, Cl-, I-, Fe2+, sulfate and phosphate. The present study, therefore, provides information for further investigation of the mechanism of lactation-induced transport adaptation in mammary epithelial cells.

The impact of fluoroscopic confirmation of thoracic imaging on accuracy of thoracic epidural catheter placement on postoperative pain control.

BACKGROUND: Thoracic epidural analgesia (TEA) provides superior postoperative pain control compared to parenteral opioids after major thoracic and abdominal surgeries. However, some studies with respect to benefits of continuous TEA have shown mixed results. The purpose of this study was to determine the rate of successful TEA catheter insertion into the epidural space using contrast fluoroscopy and the impact of placement location on postoperative analgesia and opioid use. PATIENTS AND METHODS: After Advocate health care institutional review board approval, we conducted a prospective, open-label, single intervention study on patients undergoing thoracic or upper abdominal surgery. A thoracic paramedian epidural approach and a loss of resistance to saline technique were used to place an epidural catheter above the T11 level and fluoroscopic images with injected contrast were taken to locate the catheter tip in the epidural space. RESULTS: Twenty-five subjects were included in the study, of which 3 catheters (12%) were not identified as being in the epidural space. We found an average difference of 1.5 vertebral levels between clinical and radiological assessments of catheter tips. Thirteen catheters (52%) were more than 1 vertebral level away from the clinically assessed level. No significant difference was found in the pain scores at 1, 24, and 48 hours after surgery between patients with correct versus incorrect catheter placement. Less opioids were used in the correct catheter placement group at 24 hours (256 morphine milligram equivalent [MME] vs 201 MME) and at 48 hours after surgery (250 MME vs 173 MME), but it was not statistically significant (p=0.149 and p=0.068, respectively). CONCLUSION: Improvement in assuring success in the technique for TEA catheter placement following major thoracic or upper abdominal surgery exists, for which contrast-enhanced fluoroscopy might be a promising solution.

Perineural dexamethasone added to local anesthesia for brachial plexus block improves pain but delays block onset and motor blockade recovery.

BACKGROUND: Multiple studies have shown that perineural dexamethasone improves postoperative analgesia. However, some studies have shown minimal benefit, and have raised concerns regarding adverse physio-chemical effects of perineural dexamethasone. Furthermore, there is a paucity of studies wherein control (IV) dexamethasone was considered. OBJECTIVE: The purpose of this meta-analysis was to evaluate the effectiveness of different concentrations of perineural dexamethasone injection on postoperative analgesia, as well as complications from its use for brachial plexus blocks. METHODS: A systematic literature search was conducted using the Cochrane Central Registry of Controlled Trials, PubMed, and Scopus. Trials comparing control and local dexamethasone-treated groups, and those which reported duration of analgesia and/or pain scores/opioid consumptions were selected. Meta-analysis was performed using the Review Manager (RevMan) software 5.1. RESULTS: Fourteen studies consisting of a total of 1,022 patients were included. Perineural dexamethasone significantly prolonged the duration of postoperative analgesia in patients receiving both low-dose (4 - 5 mg) [SMD 2.41 (95% CI: 1.47, 3.35 P = 0<0.00001) I² = 82%], and higher-doses (8 - 10 mg) [SMD 4.46 (95% CI 3.54, 5.38 P < 0.00001) I² = 94%]. However, the duration of motor block was also prolonged [SMD 2.52 (95% CI: 1.06, 3.98 P = 0.0007) I² = 97%] and dexamethasone delayed latency of onset of sensory [SMD -0.49 (95% CI: -0.89, -0.09 P = 0.02) I² = 76%] and motor [SMD -0.56 (95% CI: -1.13, 0.00 P = 0.05) I² = 87%] blocks. Postoperative pain scores were improved at both 24 hours [SMD -1.46 (95% CI: -2.43, -0.50 P = 0.003) I² = 95%] and 48 hours [SMD -1.20 (95% CI: -2.26, -0.13 P = 0.03) I² = 95%] in dexamethasone-treated groups, whereas opioid consumption was reduced only at 48 hours [SMD -2.97 (95% CI: -4.17, -1.76 P < 0.00001) I² = 88%]. Complications were comparable between control and dexamethasone-adjuvant groups, except for the excessively prolonged nerve block that was observed predominantly in the dexamethasone-adjuvant group. LIMITATIONS: The limitations include different definitions used for the measurements of certain parameters such as the duration of analgesia and duration of motor block, number of studies assessing certain parameters having high heterogeneity, and varying types of local anesthetics used in various studies. CONCLUSIONS: Perineural dexamethasone addition to local anesthetic solutions significantly improved postoperative pain in brachial plexus block without increasing complications. However, perineural adjuvant dexamethasone delayed the onset of sensory and motor block, and prolonged the duration of motor block. Smaller doses of dexamethasone (4 - 5 mg) were as effective as higher doses (8 - 10 mg).

A rare case of delayed subarachnoid anesthetic blockade effects in a 103-year-old female patient.

BACKGROUND: The elderly represent a unique challenge for the effects of regional anesthesia, and very few cases of block onset delay have been described. Their delayed response is attributed to a number of factors that include: Physiologic deterioration, musculoskeletal contractures, degenerative joint disease, autonomic regulatory dysfunction, cognitive dysfunction, altered pharmacokinetics, and pharmacodynamics of local anesthetics and adjuvants. CASE DESCRIPTION: In this report we present the rare case of 45-min delay between the administration and onset of action of a subarachnoid blockade in a 103-year-old female, who was scheduled for left hip pinning, for repair of a femoral neck fracture. Patient received an injection of hyperbaric bupivacaine, 1.5 ml of 0.75% (11.25 mg), with 15 mcg of fentanyl into the subarachnoidal space and underwent the surgical procedure without complications. CONCLUSIONS: Delayed responses to subarachnoid anesthesia can be expected in extremely elderly patients. Anesthetic procedures should be monitored and managed on a case-by-case basis.

Reprogramming of in situ spinal cord stimulator for covering newly developed postthoracotomy pain.

The objective of this case report is to describe the use of in situ spinal cord stimulator (SCS) for postthoracotomy pain syndrome (PTPS). We report a 39-year-old woman with complex regional pain syndrome type I of the left lower extremity. The patient's pain was relieved by a SCS for 1 month before the patient developed slipping rib syndrome at her T12 rib from an unrelated trauma. After failed conservative treatments and undergoing a thoracotomy procedure, the patient developed PTPS. Conservative management with medications and intercostal nerve blocks provided short-term relief. An already implanted single Octrode with Eon Mini generator (St Jude Neuromodulator, Plano, TX) at the T7 level was reprogrammed in attempt to recruit peripheral fibers to target the patient's additional areas of chest discomfort. This adjustment improved the pain at the left lateral rib area as well as her left leg. The patient was followed for 1 year, and her quality of life improved since her initial presenting symptoms. The use of the SCS in this patient provided significant lasting pain relief for both complex regional pain syndrome and PTPS. We believe that the use of SCS should be considered as a treatment option for patients with PTPS to avoid side effects associated with medications and to provide long-term pain relief.

Prolactin and dexamethasone regulate second messenger-stimulated cl(-) secretion in mammary epithelia.

Mammary gland ion transport is essential for lactation and is regulated by prolactin and glucocorticoids. This study delineates the roles of prolactin receptors (PRLR) and long-term prolactin and dexamethasone (P-D)-mediation of [Ca(2+)](i) and Cl(-) transport in HC-11 cells. P-D (24 h) suppressed ATP-induced [Ca(2+)](i). This may be due to decreased Ca(2+) entry since P-D decreased transient receptor potential channel 3 (TRPC3) but not secretory pathway Ca(2+)-ATPase 2 (SPCA2) mRNA. ATP increased Cl(-) transport, measured by iodide (I(-)) efflux, in control and P-D-treated cells. P-D enhanced I(-) efflux response to cAMP secretagogues without altering Cl(-) channels or NKCC cotransporter expression. HC-11 cells contain only the long form of PRLR (PRLR-L). Since the short isoform, PRLR-S, is mammopoietic, we determined if transfecting PRLR-S (rs) altered PRLR-L-mediated Ca(2+) and Cl(-) transport. Untreated rs cells showed an attenuated [Ca(2+)](i) response to ATP with no further response to P-D, in contrast to vector-transfected (vtc) controls. P-D inhibited TRPC3 in rs and vtc cells but increased SPCA2 only in rs cells. As in wild-type, cAMP-stimulated Cl(-) transport, in P-D-treated vtc and rs cells. In summary, 24 h P-D acts via PRLR-L to attenuate ATP-induced [Ca(2+)](i) and increase cAMP-activated Cl(-) transport. PRLR-S fine-tunes these responses underscoring its mammopoietic action.

Regulation of Ca2+ mobilization by prolactin in mammary gland cells: possible role of secretory pathway Ca2+-ATPase type 2.

Regulatory role of prolactin (PRL) on Ca2+ mobilization in human mammary gland cell line MCF-7 was examined. Direct addition of PRL did not affect cytoplasmic Ca2+ concentration ([Ca2+]i); however, treatment with PRL for 24h significantly decreased the peak level and duration time of [Ca2+]i elevation evoked by ATP or thapsigargin (TG). Intracellular Ca2+ release by IP3 or TG in permeablized cells was not decreased after PRL-treatment, indicating that the Ca2+ release was not impaired by PRL treatment. Extracellular Ca2+ entry evoked by ATP or TG was likely to be intact, because entry of extracellular Ba2+ was not affected by PRL treatment. Among Ca2+-ATPases expressed in MCF-7 cells, we found significant increase of secretory pathway Ca2+-ATPase type 2 (SPCA2) mRNA in PRL-treated cells by RT-PCR experiments including quantitative RT-PCR. Knockdown of SPCA2 by siRNA in PRL-treated cells showed similar Ca2+ mobilization to that in PRL-untreated cells. The present results suggest that PRL facilitates Ca2+ transport into Golgi apparatus and may contribute the supply of Ca2+ to milk.