A recent study published in Anesthesia & Analgesia reports that postoperative pain control is improved in patients going through hip replacement surgery, due to the use of a wound catheter to deliver local anesthetic directly to the hip joint.
Researchers set out to investigate “the impact of a continuous wound infusion with ropivacaine 0.3% on pain and morphine consumption after minimally invasive hip arthroplasty”.
The double-blind study looked at a total of 76 patients who were to undergo minimally invasive hip replacement with the use of spinal anesthesia. After placement of the catheter and before closure of the wound, either 20 ml ropivacaine 0.3% or 20 ml NaCl 0.9% was (randomly) administered into the patient‘s wound in the form of a bolus. Patients receiving the 20 ml NaCl 0.9% formed the placebo group or (P-group) and those receiving 20 ml ropivacaine 0.3% were referred to as the R-group.
Using an elastomeric pump, patients received a continuous infusion of either ropivacaine 0.3% or placebo for 48 h at a rate of 8 ml/h. Patients were also offered “morphine IV patient-controlled analgesia.” In the 48-h period, investigators analyzed the morphine intake of each patient, the total as well as the unbound ropivacaine plasma concentration, along with the patients‘ pain at rest and with movement. At 3 months, a postoperative follow-up was carried out.
Results demonstrated that the mean morphine consumption was “significantly lower” in the R-group compared with the P-group, over the 48-h study period. Additionally, in the R-group, pain scores at rest and at motion were lower, and the mean patient satisfaction was higher. No toxic levels of ropivacaine were seen in the R-group.
Results from the 3-month postoperative follow-up demonstrated that analgesic intake and hip pain were similar between both the placebo and the ropivacaine 0.3% groups. However, investigators did see a “significant reduction” in both ‘discomfort‘ felt when touching and applying pressure to the wound in the R-group.
Commenting on the study, Steven Shafer (Columbia University, NY, USA) states, “Wound catheters are very inexpensive and highly effective. This is an important advance in providing high quality pain relief with minimal cost.”
Authors of the study conclude that “continuous epicapsular wound infusion with ropivacaine 0.3% after minimally invasive hip replacement is an efficient technique for reducing morphine consumption and improving the quality of post-operative analgesia.” The report also demonstrates that the positive effects of this specific technique can still be observed at 3 months postsurgery.
– Written by Roshaine Gunawardana
Sources: Aguirre J, Baulig B, Dora C et al. Continuous epicapsular ropivacaine 0.3% infusion after minimally invasive hip arthroplasty: a prospective, randomized, double-blinded, placebo-controlled study comparing continuous wound infusion with morphine patient-controlled analgesia. Anesth. Analg. 114(2), 456–461 (2012); International Anesthesia Research Society (IARS): http://newswise.com/articles/local-anesthetic-stops-pain-at-the-source-after-hip-replacement-surgery
According to a report by Global Industry Analysts, Inc., at present, “more than 1.5 billion people worldwide suffer from chronic pain of varying degrees.” A specific form of chronic pain, termed neuropathic pain, is caused by damage to the nervous system and can be most commonly located in the legs and back. The same report states that, “Approximately 3–4.5% of the global population suffers from neuropathic pain, with incidence rate increasing in complementary to age.”
Researchers from The Scripps Research Institute (CA, USA) have uncovered a major clue in the understanding of neuropathic pain. By using a novel approach known as metabolomics, the study investigators identified that the small molecule dimethylsphingosine (DMS) is produced at abnormally high levels in the spinal cords of model rats exhibiting neuropathic pain. DMS was additionally found to cause pain when injected into the spinal cord of rats. Taken together, these findings suggest that inhibiting DMS may provide a potential treatment target for this form of chronic pain.
Lead author of the study, Gary J Patti, now an assistant professor of genetics, chemistry and medicine at Washington University (MO, USA) commented, “We think that this is a big step forward in understanding and treating neuropathic pain, and also a solid demonstration of the power of metabolomics.” The report on the study has now been published online in Nature Chemical Biology.
Metabolomics, the study of the levels of small molecule metabolites, is being increasingly used to identify biological markers or signatures of disease. “The idea was to apply metabolomic analysis to understand the biochemical basis of the neuropathic pain condition and reveal potential therapeutic targets,” explained Gary Siuzdak, a senior investigator in the study and professor of chemistry and molecular biology at the Scripps Research Center for Metabolomics (CA, USA). “We call this approach ‘therapeutic metabolomics‘”.
The investigators began by sampling segments of a previously injured tibial leg nerve, triggering neuropathic pain in a rat model, as well as rats‘ blood plasma and tissue from the spinal cord. These investigations led to the unexpected finding that nearly all of the major abnormalities in metabolite levels were present in the “dorsal horn” region of the spinal cord. “After the nerve is damaged, it degrades and rebuilds itself at the site of the injury, but remodeling also occurs, possibly over a longer period, at the terminus of the nerve where it connects to dorsal horn neurons,” Patti said.
After testing which of these abnormally altered metabolites of the dorsal horn tissue were capable of evolving signs of pain signaling in cultures of rat spinal cord tissue, DMS was identified. DMS, a major building block for the insulating sheaths of nerve fibers seems to contribute to pain at least in part by stimulating the release of proinflammatory molecules from astrocytes.
The results of this study have encouraged Patti and colleagues to test a range of inhibitors of DMS production in the hope that they may prove to be effective treatments or prevent the onset of neuropathic pain.
– Written by Paolo Reveglia
Sources: Patti GJ, Yanes O, Shriver LP et al. Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin. Nat. Chem. Biol. doi:10.1038/nchembio.767 (2012) (Epub ahead of print); The Scripps Research Institute – News Releases: www.scripps.edu/news/press_releases/20120122siuzdak.html; Global Industry Analysts, Inc.: www.strategyr.com/pressMCP-1130.asp
Painful flat feet is a condition commonly affecting middle-aged women over 40 years of age. It is caused by a gradual stretching, over time, of the posterior tibialis tendon (PTT), which stabilizes the arch of the foot. Risk factors for the condition include obesity, hypertension and diabetes, and it is thought to be potentiated by wearing high heels and standing for long periods.
A recent study published in the Annals of the Rheumatic Diseases investigated the causes of adult acquired flat foot secondary to a dysfunctional PTT tendon. Anthony Corps (Addenbrooke‘s Hospital, Cambridge, UK) and colleagues investigated the differences in the structure and composition of tendons in people with a healthy PTT, people with a dysfunctional PTT and people with a replacement flexor digitorum longus tendon. The samples of dysfunctional and replacement tendons were taken from patients undergoing surgical reconstruction. Samples were taken and analyzed for collagen and glycosaminoglycan, pentosidine, and collagen crosslinks. Total RNA was also analyzed for mRNA encoding for MMPs and matrix proteins using real-time, reverse transcription PCR.
In the dysfunctional PTT it was seen that there were higher levels of collagen, glycosaminoglycan, aggrecan, biglycan and MMP2 and MMP23, whereas lower levels of pentosidine were seen compared with the healthy and replacement tendons. The replacement tendons were similar to healthy tendons; however, collagen had fewer ketamine and more aldimine cross-links than the healthy or dysfunctional PTTs. It was also shown to have lower levels of MMP3 and ADAM with thrombospondin domain-5 mRNA as did the dysfunctional tendon. The replacement tendon however, had higher levels of the ADAM thrombospondin domain-1 than the dysfunctional tendon.
The changes seen in the dysfunctional PTT compared with the healthy tendons were consistent with chronic remodelling of the extracellular matrix. The current treatment for this condition is surgery; however, it has been postulated that these findings regarding altered enzyme activity in the dysfunctional tendons could reveal a target for new drug therapies in the future. Further research is needed to discover which specific enzymes should be targeted and whether people could be genetically predisposed to the condition. This research could, however, take 10–15 years.
Similar changes in enzyme activity have also been observed in patients with Achilles tendonitis and so these results may help in the search for an alternative treatment to surgery for these patients as well.
– Written by Claire Attwood
Sources: Corps AN, Robison AHN, Harrall RL et al. Changes in matrix protein biochemistry and the expression of mRNA encoding matrix proteins and metalloproteinases in posterior tibialis tendinopathy. Ann. Rheum. Dis. doi:10.1136/annrheumdis-2011–200391 (2011) (Epub ahead of print); University of East Anglia Media room: First step towards treatment for painful flat feet www.uea.ac.uk/mac/comm/media/press/2012/January/flatfeet
A previously unknown effect of opioids has been revealed by Ruth Drdla-Schutting (Centre for Brain Research, Medical University of Vienna, Austria) and colleagues. The study published recently in Science shows that opioids can remove the memory of pain in the spinal cord, which could help to eliminate a key cause of pain.
The pain memory tract is triggered by multiple mechanisms, one being long-term potentiation at C-fiber synapses that causes hyperalgesia. The pain memory can result in the sensation of amplified pain lasting much longer than the cause of the pain, this can eventually lead to a condition known as chronic pain syndrome.
Opioids are usually used to treat pain and are administered at a moderate dose continually, they are able to bind specifically to µ-opiate receptors, which are found on C fibers. This causes depression of the pain processing systems during the period of medication, which stops once medication is terminated.
In the study, the investigators recreated a surgical procedure in vivo in which pain fibers were stimulated under control conditions. This study was based on the ability of opioids to bind specifically to the µ-opiate receptors. Test subjects were given a high dose of an opioid (morphine or morphine analogue) over 60 min. The high doses of opioids were found to reverse cellular changes and the long-term potentiation at the C fibers causing depotentiation. This involved calcium-dependant signaling and normalization of the phosphorylation state of the α-amino-3-hydroxy-5-methy-4-isoxazolepropionic acid receptors. This was shown to reverse hyperalgesia, erase the spinal memory tract of pain and switch off the amplification of pain
Quoted on the university press release Jürgen Sandkühler (Medical University of Vienna) states “If our approach turns out to be effective under clinical conditions, this would herald a paradigm shift in pain therapy. It would mean moving away from the temporary, purely symptom-based pain therapy to a long-term removal of the cause of pain based on pain mechanisms using opioids.”
– Written by Claire Attwood
Sources: Drdla-Schutting R, Benrath J, Wunderbaldinger G, Sandkühler J. Erasure of a Spinal memory trace of pain by a brief, high-dose opioid administration. Science 334(6065), 235–238 (2011); Medical University of Vienna news room: Opioids erase memory traces of pain: www.meduniwien.ac.at/homepage/news-and-topstories/en/?tx_ttnews%5Btt_news%5D=1999&cHash=e01ca60db4
News released by ProStrakan, Inc. reports the US FDA approval of a shared Risk Evaluation and Mitigation Strategy (REMS) program for all transmucosal immediate release fentanyl (TIRF) pain treatments.
The REMS is to include all TIRF products, such as Abstral®, a rapidly-disintegrating sublingual tablet. Abstral was FDA-approved in January 2011 for use specifically in the “management of breakthrough pain in cancer patients 18 years of age and older who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain.”
Opioids are effective analgesics for pain reduction, however, they are also associated with dependence, tolerance, abuse and misuse in some individuals. The TIRF REMS Access program intends to decrease the risk of “misuse, abuse, addiction, overdose and serious complications due to medication errors.” The program aims to achieve this by ensuring that TIRF medicines are prescribed and dispensed to the correct patients (including use only in opioid-tolerant patients), stopping any incorrect conversion between fentanyl products, as well as by “preventing accidental exposure to children and others for whom it was not prescribed,” and lastly by “educating prescribers, pharmacists and patients on the potential for misuse, abuse, addiction and overdose of TIRF medicines.”
This new system will go live in March 2012 and will then be possible for groups such as prescribers, patients and pharmacies to be registered for one single program for these specific products, rather than being part of several different REMS depending on the TIRF product that they are associated with, as is the case at present.
– Written by Roshaine Gunawardana
Source: ProStrakan – Media Centre: www.prostrakan.com/__data/assets/pdf_file/0019/7435/FINALAbstral_Shared_REMS_Release_12_29_11.pdf