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Researchers Say Answer to Chronic Pain May Start With B-Vitamins

ProHealthNetwork.com 04-28-2003

New Findings Reveal That This Treatment Could Be Highly Effective In Alleviating Pain Caused By Injury to the Nervous System

DALLAS, April 14 /PRNewswire/ --

Chronic pain affects some 86 million Americans a year and accounts for about $90 billion lost annually due to sick time, reduced productivity, and direct medical and other benefit costs. Many who suffer from chronic pain are told to learn to "live with it." Now new research indicates that relief may be found at the vitamin counter in your neighborhood grocery story.

Researchers in the Research Institute at Parker College of Chiropractic in Dallas, Texas, say they may have found an effective treatment for various painful conditions caused by injuries to the nervous system. Tests using B-vitamins, such as B1, B6, and B12, are showing significant results in blocking pain in laboratory rats.

Xuejun Song MD, PhD, Associate Professor and Associate Director of Basic Science Research, and Zhengbei Wang, MD, Postdoctoral Associate, both from the Parker Research Institute, are presenting their findings this week at the Experimental Biology meeting in San Diego (April 11-15, 2003) held by The American Physiological Society (APS) and the other five prestigious national research organizations. APS has identified the Parker team's study--one of thousands submitted from worldwide scientists--as one of the twelve that may hold potential interest for the public.

Dr. Song heads the research team, which conducted tests ranging 2-12 weeks to examine the short- and long-term effects of B-vitamins on rats that had been put through invasive operative procedures. The team's results found that both severity and duration of pain in these rats were significantly reduced depending on the dosage.

"These studies strongly support and broaden the knowledge and clinical use of B-vitamins in aiding in treatment of chronic pain due to the nerve injury or spinal cord trauma and/or other injuries and diseases of the nervous systems," noted Song.

Xuejun Song, MD, PhD Dr. Song is Associate Professor, Associate Director of Basic Science Research, Parker College Research Institute. He received his MD in medicine from Xuzhou Medical College, P.R. China, and his PhD in Neurobiology from the Shanghai Brain Research Institute, Chinese Academy of Sciences. Dr. Song conducted his post-doctorate studies in anesthesiology and neurobiology at Yale University School of Medicine.

In his 17 year medical career, Dr. Song has been an instructor in the Department of Integrative Biology, Pharmacology and Physiology at The University of Texas-Houston Medical Center and a Senior Scientist, Associate Professor, Head of Laboratory of Electrophysiology at Parker College before taking on his present role as a director at Parker College's Research Institute.

Dr. Song is an active member of many academic organizations including the Society for Neuroscience, the American Society of Physiology, the International Association for Study of Pain, the International Brain Research Organization, and the American Advanced Association of Sciences.

About Parker College of Chiropractic Parker College of Chiropractic, located in Dallas, is one of the country's leading educators of healthcare professionals with an international student enrollment. Founded in 1982, this private, non-profit educational institution prepares men and women to become Doctors of Chiropractic. Parker College is accredited by both the specialized professional accreditation agency, the Commission on Accreditation (C.O.A.) and the regional accreditation agency, the Commission on Colleges of the Southern Association of Colleges and Schools (S.A.C.S.). For additional information about Parker College of Chiropractic, visit the college's website at http://www.parkercc.edu .

About the American Physiological Society The American Physiological Society (APS) is one of the world's most prestigious organizations for physiological scientists. These researchers specialize in understanding the processes and functions underlying human health and disease. Founded in 1887 the Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals each year.

The Study in Detail To provide experimental evidence that supports clinical use of the B-vitamins in aiding in the treatment of chronic pain especially neuropathic pain due to primary sensory neuron injury, the present study examined antinociceptive effect of vitamin B1, B6 and B12 using the neuropathic pain model of chronic compression of DRG (CCD, Song et al. J Neurophysiol 1999, 82: 3359-3370), and the possible contributions of cGMP-PKG signaling pathway to B1 induced antinociception.

The authors of "Antinociceptive Effects of Thiamin, Pyridoxine and Cyanocobalamin in Rats with Primary Sensory Neuron injury" and "Activation of cGMP-PKG Signaling Pathway Mediates Thiamin Induced-Inhibition of Thermal Hyperalgesia in Rats with Primary Sensory Neuron Injury" are Xue-Jun Song MD, PhD, Associate Professor and Associate Director of Basic Science Research Department of Neurobiology, and Zheng-Bei Wang, MD, both from the Parker Research Institute, Dallas, TX. They are presenting their findings at the American Physiological Society conference, Experimental Biology 2003, being held April 11-15, 2003, at the San Diego Conference Center, San Diego, CA.

Methodology Experiments were performed on adult, male Sprague-Dawley rats weighing 200-250 g. CCD was produced by surgically implanting stainless steel rods unilaterally into the intervertebral foramen at L4 and L5 as we previously described. In brief, the rats were anesthetized with sodium pentobarbital (40mg/kg, i.p.), the paraspinal muscles were separated from the mammillary and transverse processes and the intervertebral foramina of L4 and L5 exposed.

A stainless steel L-shaped rod, 4 mm in length and 0.6 mm in diameter, was implanted into each foramen, one at L4 and the other at L5. Each insertion was guided by the mammillary process and transverse process. As the rod was moved over the ganglion, the ipsilateral hind leg muscles typically exhibited one or two slight twitches. After surgery, the muscle and skin layers were sutured. An oral antibiotic, Augmentin, was administered after surgery in the drinking water for each rat (7.52 g in 500 ml) for seven days.

The presence of thermal hyperalgesia was determined by measuring foot withdrawal latency to heat stimulation of surface of hindpaw. The rats were tested on each of 2 successive days prior to surgery.

Postoperative tests were conducted 1, 3, 5, 7, 10, 14 days after surgery and then once weekly for ~10 weeks in some rats for examining the long-term effects of B vitamins. For examining short-term effects, tests were conducted for up to 14 days and additional tests 2, 6, 12, 24 and 36 hours after injection of B vitamins on the third day after surgery.

The rats in different groups each received one of the following treatments via i.p. or i.t. I.p. treatments (0.1 ml/100g): (1) saline (0.9% NaCl); (2) B1 (5, 10 and 33 mg/kg, respectively); (3) B6 (5, 10 and 33 mg/kg, respectively); (4) B12 (0.05, 0.2 and 0.5 mg/kg); (5)complex B vitamins (CBV) (B1+ B6 + B12 at different doses); (6) CBV for 7 consecutive days aftersurgery. I.t. treatments (20 *l): (1)saline; (2) B1 (33, 66 and 132 *g); (3) PKG inhibitor Rp-8pCPT-cGMPS (0.1 and 1 *M) +B1 (66 *g); (4) guanylylcyclase inhibitor ODQ (0.02 and 0.2 *M) + B1; (5) cGMP analog 8Br-cGMP (0.1 and 1 *M); (6) PKG activator SP-cGMP (0.1 and 1 *M); (7) Rp-8pCPT-cGMPS + 8Br-cGMP; (8) Rp-8pCPT-cGMPS + SP-cGMP; (9) B1 66 *g for 7 consecutive days after surgery. Additional rats were used as sham or unoperated control.

Results B1, B6, B12 and their combination, i.p. or i.t., significantly inhibited thermal hyperalgesia (pain) evidenced by reversal of the shortened latency of foot withdrawal to noxious heat stimulation ipsilateral to CCD. This inhibition was in dose-dependent manner. Hyperalgesia was inhibited about 20-100 percent at 2, 6 and 12 hr, and recovered at 24 or 36 hr test dependent on different doses.

Repetitive application of CBV for seven days produced long-term inhibitory effects on thermal hyperalgesia. The extreme sensitivity to stimuli disappeared four to five weeks after injury in rats with CBV treatment. In contrast, hyperalgesia lasted for eight to ten weeks in rats with saline or without any treatment. In addition, we found that combination of threshold doses of individual of the vitamins produced a synergetic inhibitory effect on thermal hyperalgesia.

B1, i.t., induced-inhibition of hyperalgesia was reversed by inhibitors of cGMP-PKG signaling pathway ODQ (guanylyl cyclase inhibitor) and Rp-8pCPT-cGMP (PKG inhibitor). cGMP analog 8Br-cGMP and PKG activator SP-cGMP inhibited thermal hyperalgesia, respectively. Such inhibition is similar to that produced by B1. Rp-8pCPT-cGMP again reversed 8Br-cGMP and SP-cGMP induced- inhibition of thermal hyperalgesia. B1 and the activators and inhibitors of cGMP-PKG pathways did not alter the foot withdrawal latency in unoperated control rats.

Summary The present studies demonstrate that spinal application as well as intraperitoneal injection of vitamin B1, B6, B12 their combination can produce short- and long-term inhibition of hyperalgesia following chronic compression dorsal root ganglion neurons produced by artificial intervertebral foramen stenosis. Both severity and duration of hyperalgesia are significantly reduced. These results strongly support clinical use of B-vitamins in aiding in treatment of chronic pain and/or other diseases due to similar injuries to the nervous system. SOURCE: Parker College of Chiropractic

Reduced vitamin D levels found in chronic pain patients - from Life Extension Foundation

The December 2003 issue of Mayo Clinic Proceedings published the results of a study of 150 adults and children conducted at the University of Minnesota which found an association between persistent, nonspecific musculoskeletal pain and a deficiency in vitamin D. Chronic pain is reported by up to one-fifth of American adults and has resulted in disability at some point in the lives of the majority of those who experience it.

The study included African-American, East African, Hispanic, American Indian, Southeast Asian, and white participants with nonspecific musculoskeletal pain who did not have fibromyalgia. The investigators measured serum 25-hydroxyvitamin D levels and categorized the participants according to the degree of deficiency. They found that 93 percent of all subjects with pain were vitamin D deficient. One hundred percent of African-American, East African, Hispanic, and Native American subjects were deficient in the vitamin, as well as all subjects under the age of thirty, with 55 percent of this age group classified as severely deficient. Five participants had undetectable levels of vitamin D.

In an accompanying editorial, Michael F Holick MD of Boston University School of Medicine explained that the vitamin D deficient state results in inadequate calcium absorption. This leads to an increase in parathyroid hormone production which causes calcium to be leached from the bones, resulting in osteopenia and osteoporosis. Increased parathyroid hormone also causes increased phosphorus excretion, leading to inadequate bone mineralization, the end result of which can be bone pain. Muscle weakness and muscular aches can also be caused by vitamin D deficiency. Dr Holick stated that a minimum of 1000 international units per day of vitamin D is necessary to satisfy the body’s requirement.

Olive oil may have pain-relieving powers - Have a headache? No aspirin or ibuprofen handy? Try some olive oil -- actually, freshly pressed extra-virgin olive oil would be best, according to a group of chemists, who've discovered that it contains a compound that mimics the pain-relieving action of ibuprofen.

The compound, called oleocanthal, blocks the same pain pathway as ibuprofen, a member of the nonsteroidal anti-inflammatory drugs, Paul A. S. Breslin from the Monell Chemical Senses Center in Philadelphia and colleagues report in the journal Nature this week.

According to Breslin and colleagues, oleocanthal in newly pressed extra-virgin olive oil and ibuprofen (in solution) both produce a strong stinging sensation in the throat, an indicator of a "shared pharmacological activity, with oleocanthal acting as a natural anti-inflammatory compound that has a potency and profile strikingly similar to that of ibuprofen."

In tests conducted on different premium olive oils, the chemists found a strong positive link between levels of oleocanthal and its intensity as a throat irritant. Similar results were achieved in tests of a synthetic version of oleocanthal they created, confirming that this compound is in fact the active ingredient in olive oil.

According to the chemists, oleocanthal, like ibuprofen, inhibits so-called COX enzymes in a dose-dependent fashion -- the higher the dose the greater the inhibition.

By their calculations, a 50-gram daily dose of olive oil is equal to about 10 percent of the ibuprofen dose recommended for pain relief in an adult.

So, while it won't cure a headache, regular consumption of olive oil might have some of the long-term health benefits of ibuprofen, researchers say. The identification of an ibuprofen-like oleocanthal in olive oil also provides a possible explanation for the well known health benefits of an olive oil-rich Mediterranean diet.

"Our findings raise the possibility that long-term consumption of oleocanthal may help to protect against some diseases by virtue of its ibuprofen-like COX-inhibiting activity," Breslin and colleagues write.

For example, it's well known that aspirin, another COX blocker, protects the heart. Ibuprofen reduces the risk of developing some cancers and also prevents blood platelets from clumping together, which can block arteries. Ibuprofen has also been shown to reduce levels of an Alzheimer's disease-related protein in mice.

SOURCE: Nature, August 31, 2005.