Anti-pruritic Effect of Botulinum Toxin Type A against Histamine-induced Pruritus on Canine Skin

개에서 Histamine으로 유발한 피부소양증에 대한 보툴리늄 톡신의 항소양 효과

  • Jeong, Byung-Han (Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Tae-Wan (Laboratory of Veterinary Physiology, College of Veterinary Medicine, Kyungpook National University) ;
  • Lee, Keun-Woo (Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Oh, Tae-Ho (Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University)
  • 정병한 (경북대학교 수의과대학 수의내과학교실) ;
  • 김태완 (경북대학교 수의과대학 수의생리학교실) ;
  • 이근우 (경북대학교 수의과대학 수의내과학교실) ;
  • 오태호 (경북대학교 수의과대학 수의내과학교실)
  • Accepted : 2011.06.13
  • Published : 2011.06.30

Abstract

Botulinum toxin type A (BoNT/A) has been proven to be a safe and effective treatment for wrinkles in human. As well as the anti-wrinkle effects, the anti-pruritic effect of BoNT/A has been revealed from several researches for new therapy. The aim of this study was to investigate the anti-pruritic effect of BoNT/A against histamine-induced pruritus on canine skin. Five clinically healthy beagles were included in the study. All dogs were received 0.05 ml (5 Unit) of BoNT/A on the right dorsal thoracic region as an experiment and the same volume of saline solution was injected on the left dorsal thoracic region as a control, respectively. Intradermal histamine injections were performed four times (before treatment and days 1, 3 and 7 after BoNT/A injection). The severity of pruritus, the diameter and thickness of wheal, the erythema index and cutaneous temperature were assessed. The severity of pruritus was reduced on BoNT/A treated sides, compared with saline treated sides (p < 0.05). BoNT/A decreased wheal size, in both diameter and thickness (p < 0.05). Although, erythema index of both sides were increased after first histamine injection, BoNT/A treated sides showed the low-value as compared with saline treated sides. Cutaneous temperature was decreased significantly on BoNT/A treated sides. These results indicates that BoNT/A reduce histamine-induced pruritus on canine skin and suggested a possibility of application of BoNT/A for local intractable dermatologic problem in dogs.

보툴리늄 톡신(BoNT/A)은 사람에서 안전하고 효과적인 주름치료제로 적용되고 있으며 최근에는 주름치료효과 이외의 효능에 관한 연구가 활발히 진행되고 있다. 본 연구의 목적은 개 피부에 히스타민을 피하 주입하여 소양증을 유발한 다음 보툴리늄 톡신의 항소양 효과를 평가하는 것이다. 총 5 마리의 비글을 이용하여 우측 배측 흉부 피부에 보툴리늄 톡신 0.05 ml (5unit)를 주입한 처치부위와 좌측 배측 흉부 피부에 0.05 ml의 생리식염수를 주입한 대조부위를 비교하였다. 보툴리늄 톡신 투여 전, 투여 후 1, 3, 7일에 Histamine 을 피내주입하여 소양증을 유발하였다. 소양증의 정도, 팽진의 지름과 두께, 홍반수치 및 피부표면 온도를 측정하여 보툴리늄 톡신 주입 효과를 평가하였다. 소양증의 정도는 처치부위에서 유의하게 감소하였으며(p < 0.05) 팽진의 지름과 두께도 처치부위에서 유의하게 감소했다(p < 0.05). 홍반수치는 최초 히스타민을 피내투여한 직후에 처치부위와 대조부위에서 모두 증가했으나 대조부위에 비해서 처치부위에서 적게 증가하였다. 피부표면온도는 처치부위에서 유의하게 감소하였다(p < 0.05). 본 연구결과 보툴리늄 톡신은 개 피부에서 히스타민에 의한 소양증에 대한 항소양 효과를 보였으며 임상적으로 극심한 국소 소양증을 보이는 피부질환에 대해 적용할 수 있을 것으로 사료된다.

Keywords

References

  1. Aoki KR. Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology 2005; 26: 785-793. https://doi.org/10.1016/j.neuro.2005.01.017
  2. Arezzo JC. Possible mechanism for the effects of botulinum toxin on pain. Clin J Pain 2002; 18: S125-132. https://doi.org/10.1097/00002508-200211001-00003
  3. Braune C, Erbguth F, Birklein F. Dose thresholds and duration of the local anhidrotic effect of botulinum toxin injection: measured by sudometry. Br J Dermatol 2001; 144: 111-117. https://doi.org/10.1046/j.1365-2133.2001.03961.x
  4. Carr MN, Torres SM, Koch SN, Reiter LV. Investigation of the pruritogenic effects of histamine, serotonin, tryptase, substance P and inteleukin-2 in healthy dogs. Vet Dermatol 2009; 20: 105-110. https://doi.org/10.1111/j.1365-3164.2008.00716.x
  5. Cui M, Khanijou S, Rubino J, Aoki KR. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain 2004; 107: 125-133. https://doi.org/10.1016/j.pain.2003.10.008
  6. Davidson S, Zhang X, Yoon CH, Khasabov SG, Simone DA, Giesler GJ Jr. The itch-producing agents histamine and cowhage activate separate populations of primate spinothalamic tract neurons. J Neurosci. 2007; 27: 10007-10014. https://doi.org/10.1523/JNEUROSCI.2862-07.2007
  7. Favrot C, Linek M, Mueller R, Zini E. Development of a questionnaire to assess the impact of atopic dermatitis on health-related quality of life of affected dogs and their owners. Vet Dermatol 2010; 21: 63-69.
  8. Gazerani P, Pedersen NS, Drewes AM. Arendt-Nielsen L. Botulinum toxin type A reduces histamine-induced itch and vasomotor responses in human skin. Br J Dermatol 2009; 161: 737-745. https://doi.org/10.1111/j.1365-2133.2009.09305.x
  9. Giannantoni A, Rossi A, Mearini E, Del Zingaro M, Porena M, Berardelli A. Botulinum toxin A for overactive bladder and detrusor muscle overactivity in patients with Parkinson's disease and multiple system atrophy. J Urol 2009; 182: 1453-1457. https://doi.org/10.1016/j.juro.2009.06.023
  10. Gnirs K, Prelaud P. Cutaneous manifestations of neurological diseases: review of neuro-pathophysiology and diseases causing pruritus. Vet Dermatol 2005; 16: 137-146. https://doi.org/10.1111/j.1365-3164.2005.00457.x
  11. Greaves MW. Recent advances in pathophysiology and current management of itch. Ann Acad Med Singapore 2007; 36: 788-792.
  12. Hallett M. How does botulinum toxin work? Ann Neurol 2000; 48: 7-8. https://doi.org/10.1002/1531-8249(200007)48:1<7::AID-ANA2>3.0.CO;2-O
  13. Han SK, Mancino V, Simon MI. Phospholipase Cbeta 3 mediates the scratching response activated by histamine H1 receptor on C-fibre nociceptive neurons. Neuron 2006; 52: 691-703. https://doi.org/10.1016/j.neuron.2006.09.036
  14. Heckmann M, Heyer G, Brunner B, Plewig G. Botulinum toxin type A injection in the treatment of lichen simplex: An open pilot study. J Am Acad Dermatol 2002; 46: 617-619. https://doi.org/10.1067/mjd.2002.120455
  15. Hensel P, Austel M, Medleau L, Zhao Y, Vidyashankar A. Determination of threshold concentrations of allergens and evaluation of two different histamine concentrations in canine intradermal testing. Vet Dermatol 2004; 15: 304-308. https://doi.org/10.1111/j.1365-3164.2004.00400.x
  16. Heyer G, Hornstein OP, Handwerker HO. Reaction to intradermally injected substance P and topically applied mustard oil in atopic dermatitis patients. Acta Derm Venereol 1991; 71: 291-295.
  17. Heyer G, Vogelgsang M, Hornstein OP. Acetylcholine is an inducer of itching in patients with atopic eczema. J Dermatol 1997; 24: 621-625. https://doi.org/10.1111/j.1346-8138.1997.tb02305.x
  18. Huang W, Foster JA, Rogachefsky AS. Phrmacology of botulinum toxin. J Am Acad Dermatol 2000; 43: 249-259. https://doi.org/10.1067/mjd.2000.105567
  19. Hundley JL, Carroll CL, Lang W, Snively B, Yosipovitch G, Feldman SR, Jorizzo JL. Cutaneous sympton of dermatomyositis significantly impact patient's quality of life. J Am Acad Dermatol 2006; 54: 217-220. https://doi.org/10.1016/j.jaad.2004.12.015
  20. Ishikawa H, Mitsui Y, Yoshitomi T, Mashimo K, Aoki S, Mukuno K, Shimizu K. Presynaptic effects of botulinum toxin type A on the neuronally evoked response of albino and pigmented rabbit iris sphincter and dilator muscle. Jpn J Opthalmol 2000; 44: 106-109. https://doi.org/10.1016/S0021-5155(99)00197-5
  21. Rossbach K, Stark H, Sander K, Leurs R, Kietzmann M, Baumer W. The histamine $H_4$ recepter as new target for treatment of canine inflammatory skin disease. Vet Dermatol 2009; 20: 555-561. https://doi.org/10.1111/j.1365-3164.2009.00854.x
  22. Lin AT, Yang AH, Chen KK. Effects of botulinum toxin A on the contractile function of dog prostate. Eur Urol 2007; 52: 582-589. https://doi.org/10.1016/j.eururo.2007.03.002
  23. Marsella R, Nicklin CF. Intradermal skin test reactivity to histamine and substance P is blunted in dogs with atopic dermatitis. Vet Dermatol 2001; 12: 149-154. https://doi.org/10.1046/j.1365-3164.2001.00244.x
  24. Meyer-Lindenberg A, Wohlfarth KM, Switzer EN. The use of botulinum toxin A for treatment of possible essential blepharospasm in a dog. Aust Vet J 2003; 81: 612-614. https://doi.org/10.1111/j.1751-0813.2003.tb12503.x
  25. Morris JL, Jobling P, Gibbins IL. Botulinum neurotoxin A attenuates release of norepinephrine but not NPY from vasoconstrictor neurons. Am J Physiol Heart Circ Physiol 2002; 283: H2627-2635. https://doi.org/10.1152/ajpheart.00477.2002
  26. Oeconomou A, Madersbacher H. Botulinum neurotoxin A for benign prostatic hyperplasia. Curr Opin Urol 2010; 20:28-36. https://doi.org/10.1097/MOU.0b013e328333ac01
  27. Plant JD. Repeatability and reproducibility of numerical rating scales and visual analogue scales for canine pruritus severity scoring. Vet Dermatol 2007; 18: 294-300. https://doi.org/10.1111/j.1365-3164.2007.00608.x
  28. Rosser EJ Jr. Advances in the diagnostic and treatment of atopy. Vet Clin North Am Small Anim Pract 1999; 29: 1437-1447. https://doi.org/10.1016/S0195-5616(99)50137-X
  29. Rybnicek J, Lau-Gillard PJ, Harvey R, Hill PB. Further validation of a pruritus severity scale for use in dogs. Vet Dermatol 2009; 20: 115-122. https://doi.org/10.1111/j.1365-3164.2008.00728.x
  30. Schlereth T, Birklein F, Haack K, Schiffmann S, Kilbinger H, Kirkpatrick CJ, Wessler I. In vivo release of non-neuronal acetylcholine from the human skin as measured by dermal microdialysis: effect of botulinum toxin. Br J Pharmacol 2006; 147: 183-187. https://doi.org/10.1038/sj.bjp.0706451
  31. Shaari CM, Wu BL, Biller HF, Chuang SK, Sanders I. Botulinum toxin decreases salivation from canine submandibular glands. Otolaryngol Head Neck Surg. 1998; 118: 452-457.
  32. Simone DA, Alreja M, LaMotte RH. Phychophysical studies of the itch sensation and itchy skin ('alloknesis') produced by intracutaneous injection of histamine. Somatosens Mot Res 1991; 8: 271-279. https://doi.org/10.3109/08990229109144750
  33. Stander S, Schmelz M. Chronic itch and pain--similarities and difference. Eur J Pain 2006; 10: 473-478. https://doi.org/10.1016/j.ejpain.2006.03.005
  34. Swartling C, Naver H, Lindberg M, Anveden I. Treatment of dyshidrotic hand dermatitis with intradermal botulinum toxin. J Am Acad Dermatol 2002; 47: 667-671. https://doi.org/10.1067/mjd.2002.124605
  35. Tobin D, Nabarro G, Baart de la Falle H, van Vloten WA, van der Putte SC, Schuurman HJ. Increased number of immunoreactive nerve fibers in atopic dermatitis. J Allergy Clin Immunol 1992; 90: 613-622. https://doi.org/10.1016/0091-6749(92)90134-N
  36. Torgovnick J, Arsura E, Sethi NK, Hu CJ, Yuan RY, Sheu JJ, Apfel SC. Botulinum toxin for diabetic neuropathic pain: a randomized double-blind crossover trial: botulinum toxin for neuropathic pain? Neurology 2010; 74: 92-93. https://doi.org/10.1212/WNL.0b013e3181c77541
  37. Tugnoli V, Capone JG, Eleopra R, Quatrale R, Sensi M, Gastaldo E, Tola MR, Geppetti P. Botulinum toxin type A reduces capsaicin-evoked pain and neurogenic vasodilatation in human skin. Pain 2007; 130: 76-83. https://doi.org/10.1016/j.pain.2006.10.030
  38. Twycross R. Greaves MW, Handwerker H, Jones EA, Libretto SE, Szepietowski JC, Zylicz Z. Itch: scratching more than the surface. QJM 2003; 96: 7-26. https://doi.org/10.1093/qjmed/hcg002
  39. Wahgren CF. Itch and atopic dermatitis: clinical and experimental studies. Acta Derm Venereol Suppl (Stockh) 1991; 165: 1-53.
  40. Wallengren J. Neuroanatomy and neurophysiology of itch. Dermatol Ther 2005; 18: 292-303. https://doi.org/10.1111/j.1529-8019.2005.00041.x
  41. Wollina U, Karamfilov T. Adjuvant botulinum toxin A in dyshidrotic hand eczema: A controlled prosepctive pilot study with left-right comparison. J Eur Acad Dermatol Venereol 2002; 16: 40-42. https://doi.org/10.1046/j.1468-3083.2002.00361.x
  42. Wollina U, Konrad H, Peterson S. Botulinum toxin in dermatology-beyond winkles and sweat. J Cosmet Dermatol 2005; 4: 223-227. https://doi.org/10.1111/j.1473-2165.2005.00195.x
  43. Yosipovitch G, Greaves MW, Schmelz M. Itch. Lancet 2003; 361: 690-694. https://doi.org/10.1016/S0140-6736(03)12570-6