Pain – 3 Articles

New Understanding of Chronic Pain

Jan. 23, 2012 — Millions of people worldwide suffer from a type of chronic pain called neuropathic pain, which is triggered by nerve damage. Precisely how this pain persists has been a mystery, and current treatments are largely ineffective. But a team led by scientists from The Scripps Research Institute, using a new approach known as metabolomics, has now discovered a major clue: dimethylsphingosine (DMS), a small-molecule byproduct of cellular membranes in the nervous system. In their new study, the scientists found that DMS is produced at abnormally high levels in the spinal cords of rats with neuropathic pain and appears to cause pain when injected. The findings suggest inhibiting this molecule may be a fruitful target for drug development.

“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,” said Gary J. Patti, a research associate at Scripps Research during the study, and now an assistant professor of genetics, chemistry, and medicine at Washington University in St. Louis. Patti is a lead author of the report on the study, which appeared online in the journal Nature Chemical Biology on January 22, 2012.

Scientists who want to understand what makes diseased cells different from healthy cells have often looked for differences in levels of gene expression or cellular proteins — approaches known respectively as genomics and proteomics. Metabolomics, by contrast, concerns differences in the levels of small-molecule metabolites, such as sugars, vitamins, and amino acids, that serve as the building blocks of basic cellular processes. “These are the molecules that are actually being transformed during cellular activity, and tracking them provides more direct information on what’s happening at a biochemical level,” Patti said.
Metabolomics is increasingly used to find biochemical markers or signatures of diseases. One of the most relied-upon “metabolome” databases, METLIN, was set up at Scripps Research in 2005, and now contains data on thousands of metabolites found in humans and other organisms. However, in this case the research team hoped to do more than find a metabolic marker of neuropathic pain.

“The idea was to apply metabolomic analysis to understand the biochemical basis of the neuropathic pain condition and reveal potential therapeutic targets,” said Gary Siuzdak, a senior investigator in the study, who is professor of chemistry and molecular biology and director of the Scripps Research Center for Metabolomics. “We call this approach ‘therapeutic metabolomics’.”

The scientists began with a standard model of neuropathic pain in lab rats. Patti, Siuzdak, and their colleagues sampled segments of a previously injured tibial leg nerve triggering neuropathic pain, as well as the rats’ blood plasma and tissue from the rats’ spinal cords. The scientists then determined the levels of metabolites in these tissues, and compared them to levels from control animals.

Unexpectedly, the scientists found that nearly all the major abnormalities in metabolite levels were present not in the injured leg nerve fiber, nor in blood plasma, but in tissue from the “dorsal horn” region of the spinal cord which normally receives signals from the tibial nerve and relays them to the brain. “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.

Next, the researchers set up a test to see which of the abnormally altered metabolites in dorsal horn tissue could evoke signs of pain signaling in cultures of rat spinal cord tissue. One metabolite stood out — a small molecule that didn’t appear in any of the metabolome databases. Patti eventually determined that the molecule was DMS, an apparent byproduct of cellular reactions involving sphingomyelin, a major building block for the insulating sheaths of nerve fibers. “This is the first characterization and quantitation of DMS as a naturally occurring compound,” Patti noted. When the scientists injected it into healthy rats, at a dose similar to that found in the nerve-injured rats, it induced pain.

DMS seems to cause pain at least in part by stimulating the release of pro-inflammatory molecules from neuron-supporting cells called astrocytes. Patti, Siuzdak, and their colleagues are now trying to find out more about DMS’s pain-inducing mechanisms — and are testing inhibitors of DMS production that may prove to be effective treatments or preventives of neuropathic pain.

“We’re very excited about this therapeutic metabolomics approach,” said Siuzdak. “In fact, we’re already involved in several other projects in which metabolites are giving us a direct indication of disease biochemistry and potential treatments.”

Oscar Yanes, a postdoctoral fellow in the Siuzdak laboratory, was Patti’s co-lead author of the study, “Metabolomics Implicates Dysregulated Sphingomyelin Metabolism in the Central Nervous System During Neuropathic Pain.” The other contributors were Leah Shriver and Marianne Manchester of the University of California, San Diego (or UC San Diego) Skaggs School of Pharmacy and Pharmaceutical Sciences; Jean-Phillipe Courade, then at Pfizer, now at UCB Pharma in Belgium; and Ralf Tautenhahn of the Siuzdak laboratory.
Funding for the research was provided in part by the U.S. National Institutes of Health and the California Institute of Regenerative Medicine.

 

The effect of 300 mW, 830 nm laser on chronic neck pain: a double-blind, randomized, placebo-controlled study.

Pain. 2006 Sep;124(1-2):201-10. Epub 2006 Jun 27.

Source

Castle Hill Medical Centre, 269-271 Old Northern Road, Castle Hill, NSW 2154, Australia. rtchow@bigpond.net.au

Abstract

A randomized, double-blind, placebo-controlled study of low-level laser therapy (LLLT) in 90 subjects with chronic neck pain was conducted with the aim of determining the efficacy of 300 mW, 830 nm laser in the management of chronic neck pain. Subjects were randomized to receive a course of 14 treatments over 7 weeks with either active or sham laser to tender areas in the neck. The primary outcome measure was change in a 10 cm Visual Analogue Scale (VAS) for pain. Secondary outcome measures included Short-Form 36 Quality-of-Life questionnaire (SF-36), Northwick Park Neck Pain Questionnaire (NPNQ), Neck Pain and Disability Scale (NPAD), the McGill Pain Questionnaire (MPQ) and Self-Assessed Improvement (SAI) in pain measured by VAS. Measurements were taken at baseline, at the end of 7 weeks’ treatment and 12 weeks from baseline. The mean VAS pain scores improved by 2.7 in the treated group and worsened by 0.3 in the control group (difference 3.0, 95% CI 3.8-2.1). Significant improvements were seen in the active group compared to placebo for SF-36-Physical Score (SF36 PCS), NPNQ, NPAD, MPQVAS and SAI. The results of the SF-36 – Mental Score (SF36 MCS) and other MPQ component scores (afferent and sensory) did not differ significantly between the two groups. Low-level laser therapy (LLLT), at the parameters used in this study, was efficacious in providing pain relief for patients with chronic neck pain over a period of 3 months.

PMID:

16806710 [PubMed – indexed for MEDLINE]

 

Surgeons Report Two New Approaches to Lessen Postoperative Pain

(Taken from ScienceDaily.com, intended for human medicine audience, however the principles are good and some are interchangeable. Italics mine)

Oct. 8, 2013 — New combinations of postoperative pain treatment decreased both pain and the use of narcotic pain relievers according to two studies presented this week at the 2013 Clinical Congress of the American College of Surgeons. One pain treatment utilized the simple but nonstandard application of ice packs after major abdominal operations in patients, and the other treatment was a prolonged drug delivery method using nanotechnology in animals.

Past research has shown that postoperative pain is often under-treated  The standard pain treatment after most major (human) operations is narcotics, also called opioids, such as morphine. However, these medicines have many possible side effects, including sleepiness, constipation, and — when used long term — the risk of drug dependence. (we don’t see this issue in veterinary medicine, not in the same way, so  for now don’t worry about your pet becoming an addict!)

“A growing body of scientific evidence shows that narcotics may not be the best way to control pain,” said the principal investigator of the ice pack study, Viraj A. Master, MD, PhD, FACS, associate professor of urology at Emory University School of Medicine, Atlanta. “We now know that it is more effective to use combination treatments that reduce the amount of narcotics needed.

New use for ice following open abdominal procedures

Multiple studies have found that cryotherapy — application of ice to the surgical wound — is safe and effective at reducing pain after some types of operations, such as orthopedic procedures. However, researchers have not studied the use of cryotherapy in patients undergoing major, “open” (large-incision) abdominal operations, Dr. Master explained.

For the Emory study, Dr. Master and his colleagues compared the effect on postoperative pain of applying soft ice packs to the incision area after open abdominal operations (27 patients), versus no ice application (28 patients).

Patients in the cryotherapy group applied ice packs to the wound at desired intervals for at least 24 hours. They also had the option of taking prescribed opioids, whereas the other group received only opioids for pain relief. Twice a day the patients rated their pain intensity on a line indicating a range from no pain (zero) to severe pain (100).

The results showed that patients who used ice packs reported significantly less pain than those who did not ice their surgical wounds. On average, the cryotherapy group had about 50 percent less pain on the first and third days after the operation compared with the no-ice control group, according to the investigators. In addition, on the first postoperative day, the cryotherapy group used 22.5 percent less opioid pain medication than controls, while some patients who iced reportedly used no narcotics.

According to Dr. Master, surgeons should recommend that their patients who have open abdominal operations intermittently apply ice packs to the surgical wound, removing the ice when it becomes too cold. “An ice pack,” he said, “is safe and inexpensive, gives the patient a sense of empowerment because it is self-care, and doesn’t require high-tech devices.”

Prolonged delivery of lidocaine effective in animals

The pain treatment utilized in the second study used a high-tech device — nanoparticles — to create a controlled-release delivery system for the nonopioid numbing medication lidocaine. Although the effects of lidocaine injections usually are short-lived, nanotechnology allowed researchers at Houston Methodist Research Institute to extend the drug’s delivery time so that pain relief lasted all seven days of the study.

Led by Jeffrey L. Van Eps, MD, a research associate at the institute and general surgery resident at Houston Methodist Hospital, the research team developed an injectable hydrogel containing lidocaine. The gel also held microscopic spheres of a biodegradable polymer called polylactic-co-glycolic acid (PLGA), which the U.S. Food and Drug Administration has approved for drug delivery. This polymer acts as an “envelope” for nanoparticles — molecular-sized structures — of the mineral silica, whose spongelike holes take up the lidocaine gel, Dr. Van Eps explained.

“Nanotechnology with PLGA makes an ideal drug delivery system because we can tailor the nanoparticles to allow prolonged delivery,” Dr. Van Eps said. He said that this method re-duces or avoids side effects.
After first testing their lidocaine delivery system in the laboratory, Dr. Van Eps’ team obtained results in an animal model of postoperative pain. In groups of rats under different experimental conditions, the investigators rated the animals’ pain by measuring their withdrawal response to mechanical force applied around the surgical wound.

Rats that received lidocaine gel through the novel delivery system needed twice the amount of force to elicit a pain response compared with control rats that received no pain medication after the incision, the researchers reported. Using this same technique of measuring the pain response, the investigators reported that the lidocaine gel also was superior to daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) alone.

The best study results were seen with combination therapy using lidocaine gel and daily NSAIDs. This combination therapy reportedly showed equivalent effect to daily opioid narcotic treatment by mechanical-force withdrawal testing and superior results by daily scoring of pain-related adaptive behaviors. This finding is important because it shows that the experimental drug delivery system is not inferior to standard opioid treatment of pain, according to Dr. Van Eps.

Studies in larger animals will take place before the research team can test this therapy in patients, he said. Yet he called the new technology an “exciting potential treatment of post-surgical pain, the largest barrier to successful postoperative care.”

The research team developed and is testing the drug delivery system in the Houston Methodist Research Institute’s Surgical Advanced Technology Lab, which was created to accelerate transition of new products to the clinic.

The above story is based on materials provided by American College of Surgeons, via EurekAlert!, a service of AAAS.

Massage is Promising for Muscle Recovery

Massage Muscle Inflammation –

Feb. 1, 2012 — Researchers at McMaster University have discovered a brief 10-minute massage helps reduce inflammation in muscle.

Massage muscle inflammation! “As a non-drug therapy, massage holds the potential to help not just bone-weary athletes but those with inflammation-related chronic conditions, such as arthritis or muscular dystrophy”, says Justin Crane, a doctoral student in the Department of Kinesiology at McMaster.

While massage is well accepted as a therapy for relieving muscle tension and pain, the researchers delved deeper to find it also triggers biochemical sensors that can send inflammation-reducing signals to muscle cells. In addition, massage signals muscle to build more mitochondria, the power centres of cells which play an important role in healing.

What Happens to the Muscles During Massage?

“The main thing is that no one has ever looked inside the muscle to see what is happening with massage. This is what is novel about our study. No one has looked at the biochemical effects or what might be going on in the muscle itself,” said Crane.

“We have shown the muscle senses that it is being stretched and this appears to reduce the cells’ inflammatory response. “As a consequence, massage may be beneficial for recovery from injury.”

Crane said the McMaster researchers are the first to take a manual therapy, like massage, and subsequently test the effect using a muscle biopsy. They did this to show massage reduces inflammation, which is an underlying factor in many chronic diseases.

Crane admits his surprise that just 10 minutes of massage had such a profound effect. “I didn’t think that little bit of massage could produce that remarkable of a change. This was especially since the exercise was so robust. Seventy minutes of exercise compared to 10 of massage, it is clearly potent.”

The results hint that massage therapy blunts muscle pain by the same biological mechanisms as most pain medications. Massage therapy, therefore, could be an effective alternative.

Mitochondrial Dysfunction and Muscle Atrophy –

Dr. Mark Tarnopolsky, professor of medicine for the Michael G. DeGroote School of Medicine, oversaw the study.

Given that mitochondrial dysfunction is associated with muscle atrophy and other processes such as insulin resistance, any therapy that can improve mitochondrial function may be beneficial,” he said.

Crane said this study is only a first step in determining the best therapies for promoting recovery from a variety of muscle injuries.

He said that surprisingly the research proved one oft-repeated idea false! Massage did not help clear lactic acid from tired muscles.

The research appears in the Feb. 1 issue of Science Translational Medicine.

From ScienceDaily.com

 

Fat and Fat Reduction – 3 Articles

Fat is Pro-Inflammatory! Weight Loss Helps Relieve Pain From Arthritis (among other things!)

Copied from a recent post on the IVAPM*:

“…I would be looking for some of the non-pharmacologic strategies. You have already mentioned an important one, getting the weight off. Adipose tissue is the body’s largest endocrine organ, and it secretes, especially when in excess, a slew of nasty cytokines that essentially bathes the body – including the synovia and joints – in a soup of pro-inflammatory mediators. We have increasingly strong evidence in dogs that nothing more than weight loss will improve comfort and mobility in this species, including excellent one this year where the authors conclude “results indicate that body weight reduction causes a significant decrease in lameness from a weight loss of 6.10% onwards. Kinetic gait analysis supported the results from a body weight reduction of 8.85% onwards. These results confirm that weight loss should be presented as an important treatment modality to owners of obese dogs with OA and that noticeable improvement may be seen after modest weight loss in the region of 6.10 – 8.85% body weight”.”

Weight loss. There is no substitute. • Lago R, Gomez R, et al A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes. Osteoarthritis Cartilage. 2008 Sep;16(9):1101-9. • Impellizeri JA, Tetrick MA, Muir P. Effect of weight reduction on clinical signs of lameness in dogs with hip osteoarthritis. JAVMA 2000 Apr 1;216(7):1089-91 • Burkholder, 2001 • Mlacnik E, Bockstahler BA, Muller M, et al. Effects of caloric restriction and a moderate or intense physiotherapy program for treatment of lameness in overweight dogs with osteoarthritis. J Am Vet Med Assoc. 2006 Dec 1;229(11):1756-60. • Marshall WG, Hazewinkel, HA, Mullen D, et al. Vet Res Commun. The effect of weight loss on lameness in obese dogs with osteoarthritis. 2010 Mar;34(3):241-53

*International Veterinary Association of Pain Management

Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip bone mineral density induced by weight loss despite decline in bone-active hormones.

J Bone Miner Res.  2011; 26(12):2851-9 (ISSN: 1523-4681)

Shah K; Armamento-Villareal R; Parimi N; Chode S; Sinacore DR; Hilton TN; Napoli N; Qualls C; Villareal DT
Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO, USA.

Weight loss therapy to improve health in obese older adults is controversial because it causes further bone loss. Therefore, it is recommended that weight loss therapy should include an intervention such as exercise training (ET) to minimize bone loss. The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density (BMD) in obese older adults. One-hundred-seven older (age >65 years) obese (body mass index [BMI] ≥ 30  kg/m(2) ) adults were randomly assigned to a control group, diet group, exercise group, and diet-exercise group for 1 year. Body weight decreased in the diet (-9.6%) and diet-exercise (-9.4%) groups, not in the exercise (-1%) and control (-0.2%) groups (between-group p  <  0.001). However, despite comparable weight loss, bone loss at the total hip was relatively less in the diet-exercise group (-1.1%) than in the diet group (-2.6%), whereas BMD increased in the exercise group (1.5%) (between-group p  <  0.001). Serum C-terminal telopeptide (CTX) and osteocalcin concentrations increased in the diet group (31% and 24%, respectively), whereas they decreased in the exercise group (-13% and -15%, respectively) (between-group p  <  0.001). In contrast, similar to the control group, serum CTX and osteocalcin concentrations did not change in the diet-exercise group. Serum procollagen propeptide concentrations decreased in the exercise group (-15%) compared with the diet group (9%) (p  =  0.04). Serum leptin and estradiol concentrations decreased in the diet (-25% and -15%, respectively) and diet-exercise (-38% and -13%, respectively) groups, not in the exercise and control groups (between-group p  =  0.001). Multivariate analyses revealed that changes in lean body mass (β  =  0.33), serum osteocalcin (β  = -0.24), and one-repetition maximum (1-RM) strength (β  =  0.23) were independent predictors of changes in hip BMD (all p  <  0.05). In conclusion, the addition of ET to weight loss therapy among obese older adults prevents weight loss-induced increase in bone turnover and attenuates weight loss-induced reduction in hip BMD despite weight loss-induced decrease in bone-active hormones.

 

Fast Walking and Jogging Halve Development of Heart Disease and Stroke Risk Factors, Research Indicates

The findings indicate that it is the intensity, rather than the duration, of exercise that counts in combating the impact of metabolic syndrome — a combination of factors, including midriff bulge, high blood pressure, insulin resistance, higher than normal levels of blood glucose and abnormal blood fat levels — say the authors.
This has been proved in different studies in different ways for different reasons, mostly related to sport science and training, for many years. Don’t think you don’t have enough time to exercise 🙂

Keep in mind, though, that it’s very slow walks that bring about the benefits at the beginning of rehab, as per my homework instructions!

ScienceDaily (Oct. 8, 2012) — Daily activities, such as fast walking and jogging, can curb the development of risk factors for heart disease and stroke by as much as 50 per cent, whereas an hour’s daily walk makes little difference, indicates research published in the online journal BMJ Open.

The findings indicate that it is the intensity, rather than the duration, of exercise that counts in combating the impact of metabolic syndrome — a combination of factors, including midriff bulge, high blood pressure, insulin resistance, higher than normal levels of blood glucose and abnormal blood fat levels — say the authors.

Genes, diet, and lack of exercise are thought to be implicated in the development of the syndrome, which is conducive to inflammation and blood thickening.

The authors base their findings on more than 10,000 Danish adults, between the ages of 21 and 98, who were initially assessed in 1991-94 and then monitored for up to 10 years. All the participants were quizzed on the amount of physical activity they did, which was categorised according to intensity and duration.

At the initial assessment, around one in five (20.7%) women and just over one in four (27.3%) men had metabolic syndrome. Prevalence was closely linked to physical activity level.

Among the women, almost one in three of those who had a sedentary lifestyle had the syndrome whereas only one in 10 of those who were very physically active had it. Among men, the equivalent proportions were just under 37% and just under 14%

Of the remaining 6,088 participants without metabolic syndrome, just under two thirds (3,992) completed the fourth and final survey and assessment, by which point one in seven (15.4%; 585) had developed it.

Again, the prevalence was higher among those leading a sedentary lifestyle, with almost one in five (19.4%) affected compared with around one in nine (11.8%) of those who were very physically active.

It was not only the amount of exercise, but also the intensity which helped curb the likelihood of developing the syndrome.

After taking account of factors likely to influence the results, fast walking speed halved the risk, while jogging cut the risk by 40 per cent. But going for an hour’s walk every day made no difference.

“Our results confirm the role of physical activity in reducing [metabolic syndrome] risk and suggest that intensity rather than volume of physical activity is important,” conclude the authors.