A recent study by researchers at King’s College London (UK) suggests that a link exists between four common chronic pain syndromes (CPSs), leading the authors to propose that some people may be genetically predisposed to suffer from conditions of this type. The study examined identical and nonidentical twins and established that irritable bowel syndrome, musculoskeletal pain, pelvic pain and dry eye disease may have hereditary links. Migraine was demonstrated to have a degree of genetic susceptibility; however, it was not genetically linked to the other conditions.
The team studied more than 8000 pairs of twins using questionnaires concerning subjects’ chronic pain symptoms. The sample compared groups of identical twins and nonidentical twins, with the differences between these two groups providing important information about the heritability of the conditions.
All of the CPSs studied were more likely to be found in both twins in an identical pair than in the nonidentical group, leading the authors to suggest that each of the five syndromes are heritable. There was also a higher prevalence of CPSs in females than males, as expected.
Further analysis of different combinations of these CPSs in female twin pairs demonstrated that there were also stronger links between the syndromes in the identical group than in the nonidentical group, indicative of a genetic link between four of the conditions (migraine was excluded). This suggests a common genetic pathway for CPS in general, which was estimated to be 66% heritable.
Frances Williams (King’s College London), one of the investigators, commented: “This study is one of the first to examine the role of genetic and environmental factors in explaining the links between different CPS. The findings have clearly suggested that CPS may be heritable within families. With further research, these findings could then lead to therapies which may change the lives of those suffering with chronic pain.”
The similarities in symptoms also supports the presence of a possible genetic predisposition to CPSs, which may explain why many sufferers have more than one of these kinds of diseases. Shared symptoms, such as fatigue, memory loss and sleep disturbance, are often seen. Migraine was found to be less common with the other CPSs, so it appears to be a different disease entity and was excluded from simultaneous analysis with the other syndromes.
The overlap found between CPSs in this study is suggestive of an underlying genetic pathway being common to all CPSs and could lead to more effective, targeted therapies in the future.
– Written by Dominic Chamberlain
Source: Kings College London press release: www.kcl.ac.uk/newsevents/news/newsrecords/2014/May/Key-genetic-link-between-chronic-pain-conditions-like-IBS-discovered.aspx
A recently published paper from researchers at the University of North Carolina School of Medicine (NC, USA) suggests that a new target for treating chronic pain has been discovered: the enzyme PIP5K1C. The manuscript suggests that PIP5K1C controls the activity of cellular receptors that signal pain.
In the study, the researchers reduced the level of the enzyme and observed that the levels of a crucial lipid in pain-sensing neurons, called PIP2, was also lessened, thus decreasing pain. The team also reported that a compound named UNC3230 could dampen the activity of PIP5K1C and postulated that it could lead to a new kind of pain reliever, leading them to hypothesize the possibility of significantly reducing inflammatory pain, such as arthritis, as well as neuropathic pain.
Discussing the study, Mark Zylka, the study’s senior author, noted: “A big problem in our field is that it is impractical to block each of these receptors with a mixture of drugs. So we looked for commonalities – things that each of these receptors need in order to send a signal.” One of these mentioned commonalities was the lipid PIP2. Zylka continued: “So the question became: how do we alter PIP2 levels in the neurons that sense pain? If we could lower the level of PIP2, we could get these receptors to signal less effectively. Then, in theory, we could reduce pain.”
PIP2 can be generated by many different kinases in the body. The team found that the PIP5K1C kinase was expressed at the highest level in sensory neurons compared with other related kinases. The researchers then used a mouse model to demonstrate that PIP5K1C was responsible for generating at least half of all PIP2 in these neurons.
“That told us that a 50% reduction in the levels of PIP5K1C was sufficient to reduce PIP2 levels in the tissue we were interested in – where pain-sensing neurons are located,” Zylka commented. “That’s what we wanted to do – block signaling at this first relay in the pain pathway.”
Once the team realized they could reduce PIP2 in sensory neurons by targeting PIP5K1C, they screened approximately 5000 small molecules in order to identify compounds that might block PIP5K1C. There were a number of hits; however, UNC3230 was the strongest, leading the team to identify it as a possible drug candidate. The researchers realized that the chemical structure of UNC3230 could be manipulated in order to potentially turn it into an even better inhibitor of PIP5K1C. Experiments to do so are now underway at the University of North Carolina.
– Written by Dominic Chamberlain
Source: University of North Carolina press release: http://news.unchealthcare.org/news/2014/may/unc-researchers-find-new-target-for-chronic-pain-treatment
A study conducted by a team at Virginia Mason (WA, USA) on 80 total knee replacement patients has demonstrated that a nerve block technique that avoids the femoral nerve results in the need for less morphine and a potentially faster recovery for orthopedic surgery patients.
The team concluded that infusing pain control medication through a catheter in the adductor canal of the mid-thigh – rather than higher up near the femoral nerve – provided better pain control and prevented temporary weakness of the leg muscles. The authors note that this allows recovering patients to walk sooner with stronger legs, resulting in improved physical therapy participation. In addition, patients in the study needed less morphine to control their postsurgery pain.
Neil Hanson and David Auyong (both from the Virginia Mason) coauthored the paper. Hanson highlighted the novelty of the findings, saying: “No one in the world has shown all these possible outcomes in the same study with the adductor canal technique.” Auyong added, “Use of the adductor canal for pain-block infusion appears to improve safety and clinical outcomes, and reduces the length of time needed for hospitalization. All patients now get this nerve block at Virginia Mason as part of our standard work for knee replacement surgery.”
– Written by Dominic Chamberlain
Source: Virginia Mason press release: www.virginiamason.org/body.cfm?id=158&action=detail&ref=3865
A new Phase III clinical trial has demonstrated that noninvasive magnetic resonance-guided focused ultrasound surgery that heats cancers within the bone relieves pain and improves functioning for most patients when other treatment options are limited. The technique has been safely used to treat thousands of women with uterine fibroids. However, one of the study’s investigators, Mark Hurwitz (Thomas Jefferson University, PA, USA), commented: “This is the first Phase III study to use this technology in the treatment of cancer.”
Although commonly used to treat bone-related pain and despite being effective for most patients, not all patients experience pain relief from radiation therapy, and over time, those who do may have recurrence of pain. In addition, it is possible for a patient to receive the maximum radiation dose that can be safely delivered without fully controlling their pain.
A total of 147 patients from 17 centers around the world were enrolled in the study and randomized to undergo magnetic resonance-guided focused ultrasound surgery or a sham treatment. Patients in the former group received focused ultrasound precisely targeted to their bone tumors in order to heat the tumor tissue to between 65 and 85°C, resulting in its destruction. During each treatment, patients were monitored in real time via MRI in order to ensure that the correct tissue was targeted and the correct temperatures were reached while ensuring that heat in surrounding normal tissues and organs remained at safe levels. The control group underwent the same procedure but without the ultrasound device turned on. Finally, patients who did not respond to the placebo treatment within 2 weeks were unblinded and offered magnetic resonance-guided focused ultrasound surgery.
A total of 64% of patients experienced either no pain or a significant reduction in their pain at 3 months. Many patients were able to reduce or stop their use of opiod medications. Notably, the authors highlight that most patients experienced pain relief and improved functioning within several days of treatment.
Commenting on the study, Hurwitz noted, “It’s clear that for many of these patients, pain has a major impact on their everyday lives. This approach offers a new way to help alleviate that pain via an out-patient noninvasive procedure.”
Hurwitz opined that the next step in the research is to refine the treatment technique in order to obtain an even greater response rate and to apply radiation and thermal therapy together in the treatment of bone metastases, noting the established clinical benefits for other malignant conditions with this combination. Following on from this research, Thomas Jefferson University has opened a new program for thermal oncology within its Department of Radiation Oncology in order to provide patients with access to thermal therapies that have been shown to augment radiation treatment.
Adam Dicker, chairman of Jefferson’s Department of Radiation Oncology, commented: “The work provides cancer patients with more options for treatment of cancer pain and the opportunity for patients to reduce opioid use, which has significant side effects.”
– Written by Dominic Chamberlain
Source: Newswise press release: www.newswise.com/articles/focused-ultrasound-reduces-cancer-pain