At the end of this session, attendees will know the basis for the use of gold to treat refractory epilepsy and chronic joint pain and where to find out more.
Gold has been used in medicine for thousands of years, to reconstruct skull defects over 3000 years ago, to treat smallpox and measles in ancient China, and edible thin gold foil was and still is ingested for health benefits in Japan.1 Robert Koch the founder of modern microbiology discovered the bacteriostatic effect of gold salts in vitro on Mycobacterium tuberculosis. At that time it was believed that rheumatoid arthritis (RA) was caused by bacteria, and gold compounds were therefore administered to these patients.2 Despite the pathogenesis of RA being different from an infection, the treatment was still therapeutic and became known as chrysotherapy. It prompted investigations of the antiinflammatory effects of gold ions and salts. Chrysotherapy, however, was replaced by newer biological antiinflammatory compounds which did not have some of the nephrotoxic effects of gold sodium thiomalate, gold thiomalate and gold thioglucose. Still, when medication fails, gold salts are still used for chronic patients.3
Gold is invaluable in modern medicine because of its unique properties. Its biocompatibility and malleability lend itself to applications including reconstruction of the upper eyelid in humans after lagophthalmus, restoration of ear function, as a coating for endovascular stents, markers in catheters not to mention applications in human dentistry such as crowns, inlays and bridges.4 In veterinary medicine, it has significant potential to improve the quality of life of patients with chronic joint disease and refractory epilepsy as well as cervical instability and feline stomatitis in the author's experience. The exact mechanisms behind the therapeutic effects of gold compounds are not completely clarified, but its effect on inflammation is well established.
The Antiinflammatory Aspects of Gold Ions
Gold has a number of documented actions (Rau 2005):5
Inhibited lymphocyte proliferation and activation
Inhibited immunoglobulin production in B lymphocytes
Shift from proinflammatory Th1 to antiinflammatory Th2 cells
Reduction of infiltrating macrophages
Inhibition of antigen uptake, antigen processing, and antigen presentation
Reduction of proinflammatory cytokines
Reduction of adhesion molecules and reduced cell infiltration
Inhibition of formation
Lysis of fibroblasts
Leukocytes: chemotaxis and phagocytosis are inhibited
NF-B DNA binding inhibited
Inhibition of IKK activation
Inhibition of IB degradation
Angiogenesis: Inhibition of vascular endothelial growth factor
Lysosomal enzyme release is inhibited
Complement activation is inhibited
Danscher in 2002 reported that solid metallic gold implants inserted in vivo liberate gold ions in tissue that could then be traced and visualised in macrophages, mast cells and fibroblasts. The use of gold to treat inflammation is termed auro medication.6 Local implantation can bypass potential systemic spread of gold compounds as can occur with gold salts, thereby reducing the risk of adverse events, and Larsen et al. showed that gold particles too large to be phagocytosed could reduce inflammation after traumatic brain injury in mice.7 Gold ions are released through a process whereby macrophages attach to the "foreign body" attracting other macrophages and monocytes - the former have been shown to release cyanide which liberates ions,8 a process termed dissolucytosis.
Use in Veterinary Medicine
Gold implantation is not new in veterinary medicine. Durkes in 1992 reported the experimental use of gold using acupuncture points to treat degenerative joint disease, osteochondritis, osteochondritis desiccans, ventral spondylosis, and seizures.9 A more recent application of gold is implantation directly into a painful anatomic region such as around an arthritic joint. This technique has been used in veterinary medicine for the past decade.
Gold implantation in dogs as a method of pain treatment for osteoarthritis is increasing in popularity with several methods employed, including gold beads implanted into acupuncture points and gold wire implantation into affected areas. The technique has been described as the insertion of small (2-mm length, 1-mm diameter beads) 24-carat gold beads (purity 99.997%) inserted through the skin with long stainless steel needles (14 g) after surgical preparation of skin, 2 gold beads were dropped into each needle with forceps and a funnel made from a 2-ml syringe, a stiletto the same length as the needle pushed the beads just outside the needle tip.10
A recent study examining the effectiveness of gold implantation for pain control in canine hip dysplasia reviewed three double-blind placebo-controlled studies, three retrospective studies and five case studies; a pain-reducing effect was only demonstrated in one of three double-blind studies, there were no significant differences in the other two studies, while the case and retrospective studies reported therapeutic success. Issues with methodology of assessment of the therapeutic effect were identified in two studies.11 Seventy-eight dogs with hip dysplasia were randomised to receive 24-carat gold implanted at 5 acupuncture points or skin penetration but no implantation. The dogs were assessed at 14 days, 3 months and 6 months, and there were significantly greater improvements in mobility and greater reduction in signs of pain in the treatment group.12 A two-year followup (crossed over to a non-blinded and therefore open to bias) by the same authors showed a positive long-term and sustained effect of gold implantation.
The inflammatory changes observed on necropsy of 9 dogs treated with gold were dominated by lymphocyte infiltration, which is in agreement with studies using gold implants in humans. A typical foreign body reaction with granulomatous inflammation was not observed which is in accordance with studies involving gold and high gold alloys in humans, rats, and dogs in which granulomatous reactions are rarely reported. Although inflammation was evident around the implants, the severity of the lesions was minor compared with the hip joint osteoarthritis present in all treated dogs.13
Gold and Refractory Epilepsy
The effects of gold wire implantation in acupuncture points in dogs with uncontrolled idiopathic epileptic seizures were reported. The number and severity of seizures were measured in 15 dogs before and after treatment. After treatment, 9 of 15 dogs (60%) had at least a 50% reduction in seizure frequency during the 15-week followup.14
Potential Applications and Areas for Further Research
Carpal, tarsal, metacarpal and metatarsal and phalangeal arthrosis
OCD of the shoulder joint
This presentation concludes with an outline of recent cases treated by the author.
VIN editor: References 2, 3, and 5 are the same.
References 10 and 13 are the same.
1. Richards DG, et al. Gold and its relationship to neurological/glandular conditions. Int J Neurosci. 2002;112(1):31–53.
2. Rau R. Have traditional DMARDs had their day? Effectiveness of parenteral gold compared to biologic agents. Clin Rheumatol. 2005;24(3):189–202.
3. Rau R. Have traditional DMARDs had their day? Effectiveness of parenteral gold compared to biologic agents. Clin Rheumatol. 2005;24(3):189–202.
4. Demann ET, Stein PS, Haubenreich JE. Gold as an implant in medicine and dentistry. J Long-Term Eff Med Implants. 2005.
5. Rau R. Have traditional DMARDs had their day? Effectiveness of parenteral gold compared to biologic agents. Clin Rheumatol. 2005;24(3):189–202.
6. Danscher G. In vivo liberation of gold ions from gold implants. Autometallographic tracing of gold in cells adjacent to metallic gold. Histochem Cell Biol. 2002;117(5):447–452.
7. Larsen A, et al. Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury. Histochem Cell Biol. 2008;130(4):681–692.
8. Graham GG, Kettle AJ. The activation of gold complexes by cyanide produced by polymorphonuclear leukocytes. III. The formation of aurocyanide by myeloperoxidase. Biochem Pharmacol. 1998;56(3):307–312.
9. Durkes T. Gold bead implants. Probl Vet Med. 1992;4(1):207–211.
10. Lie K, Jaeger G, Nordstoga K, Moe L. Inflammatory response to therapeutic gold implantation in canine hip osteoarthritis. Vet Pathol. 2011;48(6):1118–1124.
11. Deisenroth A, Nolte I, Wefstaedt P. Use of gold implants as a treatment of pain related to canine hip dysplasia - a review. Part 2: clinical trials and case reports. Tierarztl Prax Ausq Kleintiere Heimtiere. 2013;41(4):244–254 (article in German).
12. Jaeger G, Larsen S, Soli N, Moe L. Double blind placebo controlled trial of the pain relieving effects of the implantation of gold beads into dogs with hip dysplasia. Vet Rec. 2006;158(21):722–726.
13. Lie K, Jaeger G, Nordstoga K, Moe L. Inflammatory response to therapeutic gold implantation in canine hip osteoarthritis. Vet Pathol. 2011;48(6):1118–1124.
14. Goiz-Marquez G, Caballero S, Solis H, et al. Electroencephalographic evaluation of gold wire implants inserted in acupuncture points in dogs with epileptic seizures. Res Vet Sci. 2009;86:152–161.