A research team from the University of Colorado Boulder (CO, USA) have discovered that using morphine for pain caused as a result of abdominal surgery may in fact prolong the pain felt by the patient. The results of their study were presented at the Annual Meeting of the Society for Neuroscience in San Diego (CA, USA).
The team determined that morphine and surgery together caused excitation of the nervous system glial cells and this excitation consequently led to extra pain signals being sent out to the nerves in surrounding regions. Indeed, previous research has shown that although morphine is an effective painkiller, it can also have the opposite of the desired effect.
Peter Grace (University of Colorado Boulder, CO, USA) explains that, “After abdominal surgery – even without using any drugs to treat the pain – the glial cells would be activated and they would contribute to the postoperative pain. What we‘re saying is, if you give them morphine, we also know that contributes to the pain. If you‘re putting both of those on top of each other, you‘re going to have a prolonged period of pain.”
It has been found that morphine not only binds to a specific neuron receptor that results in numbing or dulling the pain, but it also binds to TLR4 – a receptor in brain glial cells. Authors of the presentation explain that this initiates “proinflammatory cytokine and chemokine release that have antianalgesic effects against the classical opioid receptor-mediated analgesia.”
In the current investigation, researchers found that rats that were administered morphine 2 weeks before surgery, as a treatment for already existing pain, fully recovered from postoperative pain after 6 weeks. These rats were not given morphine after the surgery. Rats that were not administered morphine, took 2 weeks to fully recover from postoperative pain.
Further results demonstrated that rats that were given morphine after surgery for a period of 1 week took a total of 4 weeks to recover from postoperative pain. The control group recovered after only 2 weeks. Investigators examined how (+)-naloxone, a nonopioid TLR4 antagonist, affects pain in rats, using intrathecal osmotic minipumps to deliver the (+)-naloxone. Their study demonstrated that (+)-naloxone plus morphine actually eliminates the prolonged postoperative effect observed with morphine only.
Further research is required on the effects of morphine and (+)-naloxone on postoperative pain, with the aim of discovering more therapeutic options for clinicians to use along with morphine so that postoperative pain is not prolonged in the future.
Sources: Galer EL, Grace PM, Strand KA et al. Perioperative morphine administration prolongs post-operative pain: a role for TLR4 and inflammasome signalling. Presented at: Society for Neuroscience 2013, San Diego, CA, USA, 9–13 November 2013; University of Colorado Boulder press release: www.colorado.edu/news/releases/2013/11/12/using-morphine-after-abdominal-surgery-may-prolong-pain-cu-boulder
According to a study published in The Journal of Pain, survivors of breast cancer rate persistent postmastectomy pain as their most “troubling symptom.” Cancer Research UK states that in 2010 a total of “49,564 women … in the UK were diagnosed with invasive breast cancer,” and explains that female breast cancer incidence rates in the UK have increased by almost 70% since the mid-1970s. The American Cancer Society‘s estimates for breast cancer in the USA for 2013 are that “approximately 232,340 new cases of invasive breast cancer will be diagnosed in women” and “approximately 39,620 women will die from breast cancer.”
Many women with breast cancer have some form of surgery, including breast-conserving surgery and mastectomy. Some women experience neuropathic pain in the chest wall, armpit and/or arm after surgery. This pain is termed postmastectomy pain syndrome, and often does not dissipate with time. Authors describe persistent postmastectomy pain to be “increasingly recognized as a major individual and public health problem.”
Investigators set out to identify which factors play a contributory role in postmastectomy pain, including tumor size, stress, treatments and psychosocial factors. They analyzed 611 women who had had total or partial mastectomy and who were treated with chemotherapy, radiation and/or hormone therapy.
Using multiple regression analysis, the researchers observed that there were “significant and independent associations” between psychosocial factors and persistent postmastectomy pain. These psychosocial factors include anxiety, sleep disturbance and somatization. The study reports that treatment-related factors, such as tumor size, surgical type, radiation and chemotherapy, did not have a significant association with persistent postmastectomy pain.
The Authors of the study conclude that, “These data confirm previous studies suggesting that [persistent postmastectomy pain] is relatively common and provide new evidence of significant associations between psychosocial characteristics … with [persistent postmastectomy pain], regardless of the surgical and medical treatment that patients receive, which may lead to novel strategies in [persistent postmastectomy pain] prevention and treatment.”
Sources: Belfer I, Schreiber KL, Shaffer JR et al. Persistent postmastectomy pain in breast cancer survivors: analysis of clinical, demographic, and psychosocial factors. J. Pain 14(10), 1185–1195 (2013); American Pain Society, via newswise: www.newswise.com/articles/postmastectomy-pain-most-troubling-problem-for-breast-cancer-survivors; Cancer Research UK: http://publications.cancerresearchuk.org/cancerstats/statsbreast; American Cancer Society: www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-key-statistics
Fibromyalgia (FM) is a chronic pain condition that causes widespread muscular pain. Other symptoms of FM include problems with cognitive functioning, stiffness, disordered sleep and fatigue. According to NHS Choices, “In England and Wales, there could be up to 1.76 million adults with the condition.” Although FM can affect anyone, the condition is more prevalent in women than in men. The National Fibromyalgia Association quotes that experts in the field estimate that “approximately 10 million Americans and approximately 3–6% of the population worldwide suffer with FM.” In severe cases, FM can be “extremely debilitating” and have an impact on normal daily activities.
Research published in Arthritis & Rheumatism has discovered that, “FM patients exhibit disrupted brain responses to reward/punishment.” It is thought that this change in pain processing – or more specifically “reduced reward/punishment signaling in FM” – may be associated with “the augmented central processing of pain and reduced efficacy of opioid treatments in these patients.”
The authors of the research explain that although it is know that FM patients experience hyperalgesia, the actual central mechanism that results in a change in pain processing is not yet completely clear. Therefore, the results of this study could improve current understanding of FM and contribute to ongoing research in the field.
The study investigators used functional MRI to examine 31 FM patients and 14 control subjects while they received cuff pressure pain stimuli on their leg. While functional MRI was being performed, the FM patients and controls were given visual cues that altered them about “impending pain onset (pain anticipation) and pain offset (relief anticipation).”
Results demonstrated that FM patients exhibited a less “robust” response in certain regions of the brain during pain anticipation and relief. These brain areas are understood to be involved in sensory, affective, cognitive and pain-modulatory processes. Furthermore, the ventral tegmental area of the control subjects showed activation during pain anticipation and stimulation, and deactivation during relief anticipation. In the same area in FM patients, activity was significantly reduced or completely stopped during pain and anticipation of pain and relief. The ventral tegmental area of the brain is involved in reward and punishment processing.
Regarding the study, Marco Loggia (Massachusetts General Hospital and Harvard Medical School, MA, USA) explains, “In patients with [FM] there is an alteration in the [CNS] pain processing and a poor response to topical pain treatments, trigger point injections and opioids. Our study examines the disruption of brain function involved in the individual experience of pain anticipation and pain relief.”
Loggia goes on to conclude, “Our findings suggest that [FM] patients exhibit altered brain responses to punishing and rewarding events, such as expectancy of pain and relief of pain. These observations may contribute to explaining the heightened sensitivity to pain, as well as the lack of effectiveness of pain medications such as opioids, observed in these patients. Future studies should further investigate the neurochemical basis underlying these dysfunctions.”
Sources: Loggia ML, Berna C, Kim J et al. Disrupted brain circuitry for pain-related reward/punishment in fibromyalgia. Arthritis Rheum. doi:10.1002/art.38191 (2013) (Epub ahead of print); Wiley press release: Pleasure and pain brain signals disrupted in fibromyalgia patients: http://eu.wiley.com/WileyCDA/PressRelease/pressReleaseId-109776.html; NHS Choices: www.nhs.uk/Conditions/Fibromyalgia/Pages/Introduction.aspx; National Fibromyalgia Association: http://fmaware.org/site/PageServerff9b.html?pagename=media_factSheets
In a recent study, examination of 1.14 million adult nonsurgical hospital admissions has shown that during their stay, 51% of these patients were prescribed opioids (some at high doses) and researchers discovered that some of these patients (26%) received opioid medications on their day of discharge from the hospital. In describing the background to their study, the authors explain that, “Recent studies in the outpatient setting have demonstrated high rates of opioid prescribing and overdose-related deaths,” and go on to state that, “Prescribing practices in hospitalized patients are unexamined.”
Data were taken from 286 hospitals in the USA, between 1 July 2009 and 30 June 2012, and investigators found quite a high level of variation in opioid use regionally – the difference between the highest and lowest opioid prescribing regions being 37%. Shoshana Herzig (Beth Israel Deaconess Medical Center, Boston, MA, USA), first author of the study published in The Journal of Hospital Medicine explains that “this means, if you took very similar patients and admitted them to hospitals in the West and in the Northeast the patient in the West would be 37% more likely to be prescribed an opioid pain medicine than the patient in the Northeast.” Nonsurgical patients included those being treated for cancer, heart problems and musculoskeletal injuries among others.
Herzig states, “realizing that inpatient use might provide a portal to outpatient use, we were interested in looking at how opioids were being used in the hospital setting. Because patients who are undergoing surgery have a clear indication for and virtually always receive these pain medications, we did not include surgical patients in our study. Instead, we chose to examine only individuals who were admitted to the hospital for nonsurgical reasons.”
One observation made in this study was that 43% of all patients were exposed to multiple opioids while in hospital, and the average dose was approximately 68-mg oral morphine equivalents/day – a dose that Herzig describes as “a very high dose”. Furthermore, researchers found that a dose of ≥100 mg was taken by 23% of all patients on at least 1 day during their stay in hospital.
With respect to the study results, Herzig comments, “Prior studies have found that higher opioid doses are associated with a heightened risk of adverse events. Patients receiving doses of 100 mg/day or more are at substantially greater risk for serious problems, including severe breathing problems.” She goes on to explain, “Given that opioids are often tapered off rather than abruptly discontinued, this finding suggests that up to half of these patients were sent home with a prescription for opioid medication. Unless physicians are diligent about checking on other opioid prescriptions that a patient may have received in another setting, this means that patients could wind up with multiple opioid prescriptions, thus increasing the likelihood of an inadvertent overdose or other adverse event.”
Researchers also found that hospitals with higher rates of opioid prescribing had an associated higher risk of “a severe opioid-related adverse event per patient exposed.”
“Taken together, our findings really emphasize the importance of good communication between inpatient and outpatient providers. It‘s important that primary care physicians know what medications their patients have been exposed to during hospitalizations. We hope this information will prompt hospitals to take a closer look at their own opioid-prescribing practices. Looking ahead, a better understanding of the predictors of opioid-related adverse events in hospitalized patients might enable institutions to take steps to make these medications safer during hospital use,” Herzig concludes.
Sources: Herzig SJ, Rothberg MB, Cheung M, Ngo LH, Marcantonio ER. Opioid utilization and opioid-related adverse events in nonsurgical patients in US hospitals. J. Hosp. Med. doi:10.1002/jhm.2102 (2013) (Epub ahead of print); Beth Israel Deaconess Medical Center News: www.bidmc.org/News/In-Research/2013/November/Herzig.aspx
– All stories written by Roshaine Gunawardana