Effects of Bee Venom and Sweet Bee Venom Acupuncture on Functional Recovery and c-Fos Expression in the Brain after Sciatic Crushed Nerve Injury in Rats

  • Choi, Seung-Peom (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Kyung-Won University) ;
  • Song, Yun-Kyung (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Kyung-Won University) ;
  • Lim, Hyung-Ho (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Kyung-Won University)
  • Received : 2010.03.04
  • Accepted : 2010.04.27
  • Published : 2010.05.30

Abstract

Background: Peripheral nerve injuries are commonly encountered clinical problems and often result in severe functional deficit. Bee venom acupuncture has traditionally been used to treat several inflammatory diseases and chronic pain conditions. Objectives: The aims of this study were to compare the effects of bee venom (general bee venom, BV) and sweet bee venom (allergen-removed bee venom, SBV) acupuncture on the recovery rate of locomotor function, the expression of brain-derived neurotrophic factor (BDNF) in the sciatic nerve, and the expression of c-Fos in the brain following sciatic crushed nerve injury in rats, and to evaluate differences due to administration areas. Method: Walking track analysis, Western blot for BDNF and tyrosine receptor kinase B (TrkB), and immunohistochemistry for c-Fos were performed. In this study, comparative analyses of the effects of BV and SBV acupuncture in relation to administration sites, contralateral side or ipsilateral side, were conducted. Results: In the present result, sciatic function index (SFI) in walking track analysis significantly decreased following sciatic crushed nerve injury. The expressions of BDNF and TrkB in the sciatic nerve increased after induction of sciatic crushed nerve injury. C-Fos expression in the ventrolateral periaqueductal gray (vlPAG) and paraventricular nucleus (PVN) also increased. BV and SBV acupuncture treatment improved the SFI in walking track analysis. Treatment with SBV at 1mg/kg showed more potent enhancing effect on SFI compared to BV. Treatment with 1mg/kg BV or 1mg/kg SBV acupuncture suppressed the BDNF and TrkB expression in the sciatic nerve. BV and SBV acupuncture treatment also suppressed c-Fos expression in the PVN and vlPAG regions. Treatment with SBV at 1mg/kg showed more potent suppressing effect on c-Fos expression compared to BV when injected into the contralateral side of the injured nerve. Generally we could not find significant difference in the effects between contralateral side and ipsilateral side of the injured nerve. Conclusion: We have shown that BV and SBV acupuncture treatment can be used as the effective therapeutic modality to ameliorate the symptoms of sciatic crushed nerve injury.

Keywords

References

  1. Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1998; 33:87-107.
  2. Raso VV, Barbieri CH, Mazzer N, Fasan VS. Can therapeutic ultrasound influence the regeneration of peripheral nerves? J Neurosci Methods. 2005; 142:185-92. https://doi.org/10.1016/j.jneumeth.2004.08.016
  3. Kim DF. Effects of Acupuncture stimulation at Huatuo Jiaji (EX B2) points on axonal regeneration of injured sciatic nerve in rats. Thesis for the degree of doctor of philosophy in Oriental medicine. Graduate school of Dongguk university, Korea. 2007.
  4. Ahn HL, Yang MS, Shin MS, Choi JB, Kim SJ. The experimental study of electroacupuncture and Cornu Cervi Pantotrichum pharmacopuncture on pain decrease and nerve regeneration after crush injury of sciatic nerve. J Oriental Rehab Med. 2009; 19(1):39-55.
  5. Yang MS, Shin MS, An HL. The effects of Ohyaksugi-san (Wuyaoshunqi-san) and electrical acupuncture on nerve regeneration after crush injury in rat sciatic nerve. J Oriental Rehab Med. 2008; 18(4):25-37.
  6. Deung YK, Kim DH, Kang SJ. Effect of electroacupuncture on the regeneration of injured peripheral nerve. Korean J Electron Microscopy. 2002; 32(1):1-8.
  7. Song JS, Na C, Shin BC, Lee SK, Kwon YD, Song YS. Effects of Dokwal-tang (Duhuo-tang) and Jungsongouhyul pharmacopuncture on pain control and nerve regeneration after crush injury in rat sciatic nerve. J Oriental Rehab Med. 2008; 18(2):61-79.
  8. Lee DH, Youn DH, Na CS, Yoon YC. Effects of bee venom acupuncture injected at Hwando (GB30) on neuropathic pain in rats. J Korean Acupuncture & Moxibustion Society. 2005; 22(5):67-77.
  9. Kim SN, Kim SC, Choi HK, So KS, Lim JA, Hwang WJ, et al. Inhibitory effect of Scolopendrid aqua-acupuncture injected at Hwando (GB30) on neuropathic pain in rats. J Korean Acupuncture & Moxibustion Society. 2004; 21(3):145-67.
  10. Lee HJ, Kim JH, Choi JH, Park SY. Effects of oral administration of Ligigeopoonsan on neuropathic pain and c-Fos protein expression in rats. J Korean Oriental Medical Ophthalmology & Otolaryngology & Dermatology. 2005; 18(1):50- 60.
  11. Kim JH, Seol IC, Ryu HR, Jo HK, An JJ, Namgung U, et al. Facilitated axonal regeneration of injured sciatic nerves by Yukmijihwang-tang treatment. Korean J. Oriental Physiology & Pathology. 2008; 22(4):896-902.
  12. Hong SS, Oh MS. Improved axonal regeneration responses in the injured sciatic nerve of rats by Daggui treatment. J Korean Oriental Med. 2008; 29(2):133-50
  13. Jo HK, Namgung U, Seol IC, Kim YS. Growth promoting effects of Oriental medicinal drugs on sciatic nerve regeneration in the rat. Korean J. Oriental Physiology & Pathology. 2005; 19(6): 1666-72.
  14. Kim YW, Song YK, Lim HH. Effect of Amygdalin on the functional recovery and c-Fos expression in the ventrolateral periaqueductal gray region after crushed sciatic nerve injury in rats. J Oriental Rehab Med. 2006; 16(4):37-47.
  15. Han HJ, Lee HJ, Kang SS, Lee SH, Cho IH, Lee JH, et al. Effect of Red Ginseng Total Saponin on sciatic nerve regeneration. J. Ginseng Res. 2003; 27(3):103-9. https://doi.org/10.5142/JGR.2003.27.3.103
  16. Ryu MS, Song YK, Lim HH. Effect of herbal bath on functional recovery and c-Fos expression in the ventrolateral periaqueductal gray region of the brain after sciatic crushed-nerve injury in rats. Korean J Oriental Med. 2006; 27(4):116-24.
  17. Chung WS, Kim SS. The study of literature review on mechanism of bee venom therapy for musculo-skeletal disorder. J. Korea CHUNA Manual Med. 2002; 3(1):111-23.
  18. The academic committee of Korean pharmacopuncture institute. Pharmacopuncturology, the $1^{st}$ edition. Seoul: Elsevier Korea L.L.C. 2008; 167-99.
  19. Kwon KR, Choi SH, Cha BC. Component analysis of sweet BV and clinical trial on antibody titer and allergic reactions. J Korean Pharmacopuncture Institute. 2006; 9(2):77-86.
  20. Lee JS, Lee JY, Kwon KR, Lee HC. A Study on Allergic Responses between Bee Venom and Sweet Bee Venom Pharmacopuncture. J Korean Pharmacopuncture Institute. 2006; 21:61-77.
  21. Na WM, Lee SY, Jang EH, Kim SC, Moon HC. A study on pain relief effects and allergic responses for the osteoarthritis of the knee joint between sweet bee venom and bee venom pharmacopuncture. J Korean Pharmacopuncture Institute. 2007; 10(2):47-55. https://doi.org/10.3831/KPI.2007.10.2.047
  22. Kim SC, Na WM, Lee SY, Jang EH, Lim SI. A study on pain relief effects and allergic responses for the osteoarthritis of the knee joint between sweet bee venom and bee venom pharmacopuncture. J Korean Pharmacopuncture Institute. 2008; 11(1):31-40. https://doi.org/10.3831/KPI.2008.11.1.031
  23. Kim JH, Jang SH, Yoon HM, Jang KJ, Ahn CB, Kim CH, et al. The comparison of effectiveness between bee venom and sweet bee venom therapy on chronic lower back pain. J Korean Pharmacopuncture Institute. 2008; 11(4):15-24. https://doi.org/10.3831/KPI.2008.11.4.015
  24. Lee KH, Youn HM, Ko WS, Song CH, Jang KJ, Ahn CB, et al. Comparison of treatment effects and allergic responses to stiff neck between sweet bee venom and bee venom pharmacopuncture. J Korean Pharmacopuncture Institute. 2008; 11(4): 39-48. https://doi.org/10.3831/KPI.2008.11.4.039
  25. Kwon KR, Chu CS, Park HS, Kim MK, Cha BC, Lee E. Experimental studies of quantitative evaluation using HPLC and safety of sweet bee venom. J Korean Pharmacopuncture Institute. 2007; 10(2):81-6. https://doi.org/10.3831/KPI.2007.10.2.081
  26. Kwon KR, Kang KS, Lee KH, Lim CS, Jeong HS, Kwon HY. Clinical observation of anaphylaxis after treated with sweet BV. J Korean Pharmacopuncture Institute. 2009; 12(2):85-90. https://doi.org/10.3831/KPI.2009.12.2.085
  27. Song BY. A clinical study on the effects of sweet bee venom herbal acupuncture for patients with whiplash injury. J Korean Pharmacopuncture Institute. 2007; 10(3):77-83. https://doi.org/10.3831/KPI.2007.10.3.077
  28. Lee TH, Hwang HS, Chang SY, Cha JH, Jung KH, Lee EY, et al. The comparison of effectiveness between bee venom and sweet bee venom therapy on low back pain with radiating pain. J Korean Pharmacopuncture Institute. 2007; 10(3): 85-9. https://doi.org/10.3831/KPI.2007.10.3.085
  29. Cha YY. Case study on effect of sweet bee venom mesotherapy on obese female patient. Korean J. Oriental Physiology & Pathology. 2008; 22(4):982-986.
  30. Lim CS, Park WP, Jang SB, Choi YC, Kim KS, Kwon KR, et al. Clinical studies of sweet bee venom to the effect of abdominal fat accumulation. J Korean Pharmacopuncture Institute. 2008; 11 (2):33-40. https://doi.org/10.3831/KPI.2008.11.2.033
  31. Yoo HS, Kim JS. The effect of sweet bee venom pharmacopuncture (SBVP) on cancer-related pain: a randomized controlled trial and double blinded-pilot study. J Korean Pharmacopuncture Institute. 2008; 11(1):21-9. https://doi.org/10.3831/KPI.2008.11.1.021
  32. Park SH, Kim TS, Hur YJ, Kwon KR. Clinical report on the treatment of 70 molluscum contagiosum cases using sweet bee venom pharmacopuncture. J Korean Pharmacopuncture Institute. 2008; 11(2):111-6. https://doi.org/10.3831/KPI.2008.11.2.111
  33. Park IS, Yoon IJ. The clinical study on 1 case for the sensation of patient with spinal cord injury whose is improved by using sweet BV. J Korean Pharmacopuncture Institute. 2009; 12(2):77-84. https://doi.org/10.3831/KPI.2009.12.2.077
  34. Lee MH, Kim H, Lim BV, Chang HK, Lee TH, Jang MH, et al. Naloxone potentiates treadmill running-induced increase in c-Fos expression in rat hippocampus. Life Sci. 2003; 73:3139-47. https://doi.org/10.1016/j.lfs.2003.06.005
  35. Naylor RL, Robertson AG, Allen SJ, Sessions RB, Clarke AR, Mason GG, et al. A discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4. Biochem Biophys Res Commun. 2002; 291:501-7. https://doi.org/10.1006/bbrc.2002.6468
  36. De Koning P, Brakkee JH, Gispen WH. Methods for producing a reproducible crush in the sciatic and tibial nerve of the rat and rapid and precise testing of return of sensory function. Beneficial effects of melanocortins. J Neurol Sci 1986; 74:237-46. https://doi.org/10.1016/0022-510X(86)90109-7
  37. Bain JR, Mackinnon SE, Hunter DA. Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plast Reconstr Surg. 1989; 83:129-38. https://doi.org/10.1097/00006534-198901000-00024
  38. Park JH, Seo BI, Choi HS, Kim YS, Seo YB, Kang JS, et al. The effect of Morindae Radix extracts on the sciatic nerve neurectomized osteoporotic ddY mice model prevention effects. Kor. J. Herbology. 2005; 20(4):83-94.
  39. Mi YQ, Wu YC, Chen Y. Effects of warm needle moxibustion on nerve root local inflammatory factors (NOS and CGRP) in the lumbar nerve root compress model rats. Zhongguo Zhen Jiu. 2009; 29(1):48-52.
  40. Lee JD, Park HJ, Chae Y, Lim S. An overview of bee venom acupuncture in the treatment of arthritis. Evid Based Complement Alternat Med. 2005; 2(1):79-84. https://doi.org/10.1093/ecam/neh070
  41. Banks BE, Brown C, Burgess GM, Burnstock G, Claret M, Cocks TM, et al. Apamin blocks certain neurotransmitter-induced increases in potassium permeability. Nature. 1979; 22:415-7.
  42. Shuba MF, Vladimirova IA. Effect of apamin on the electrical responses of smooth muscle to adenosine 5'-triphosphate and to non-adrenergic, non-cholinergic nerve stimulation. Neuroscience. 1980; 5:853-9. https://doi.org/10.1016/0306-4522(80)90154-2
  43. Kim HW, Kwon YB, Ham TW, Roh DH, Yoon SY, Lee HJ, et al. Acupoint stimulation using bee venom attenuates formalin-induced pain behavior and spinal cord Fos expression in rats. J Vet Med Sci. 2003; 65:349-55. https://doi.org/10.1292/jvms.65.349
  44. Roh DH, Kwon YB, Kim HW, Ham TW, Yoon SY, Kang SY, et al. Acupoint stimulation with diluted bee venom (apipuncture) alleviates thermal hyperalgesia in a rodent neuropathic pain model: involvement of spinal alpha 2-adrenoceptors. J Pain. 2004; 5:297-303. https://doi.org/10.1016/j.jpain.2004.05.003
  45. Choi YC, Kwon KR, Choi SH. Purification of peptide components including melittin from bee venom using gel filtration chromatography and propionic acid/urea polyacrylamide gel electrophoresis. J Korean Pharmacopuncture Institute. 2006; 9(2):105-11. https://doi.org/10.3831/KPI.2006.9.2.105
  46. An JC, Kwon KR, Lee EH, Cha BC. Experimental study on the comparison of antibacterial and antioxidant effects between the bee venom and sweet bee venom. J Korean Pharmacopuncture Institute. 2006; 9(3):97-104. https://doi.org/10.3831/KPI.2006.9.3.097
  47. Kim MK, Lee SH, Shin JY, Kim KS, Cho NG, Kwon KR, et al. The effects of bee venom and sweet bee venom to the preadipocyte proliferation and lipolysis of adipocyte, localized fat accumulation. J Korean Pharmacopuncture Institute. 2007; 10(3):5-19. https://doi.org/10.3831/KPI.2007.10.3.005
  48. Yook TH, Yu JS, Jung HS. Effects of sweet bee venom and bee venom on the heart rate variability. J Korean Pharmacopuncture Institute. 2008; 11(1):41-54. https://doi.org/10.3831/KPI.2008.11.1.041
  49. Lee JH, Kwon YB, Han HJ, Mar WC, Lee HJ, Yang IS, et al. Bee venom pretreatment has both an antinociceptive and anti-inflammatory effect on carrageenan-induced inflammation. J Vet Med Sci. 2001; 63:251-9. https://doi.org/10.1292/jvms.63.251
  50. Kwon YB, Kang MS, Kim HW, Ham TW, Yim YK, Jeong SH, et al. Antinociceptive effects of bee venom acupuncture (apipuncture) in rodent animal models: a comparative study of acupoint versus non-acupoint stimulation. Acupunct Electrother Res. 2001; 26:59-68.
  51. won YB, Lee HJ, Han HJ, Mar WC, Kang SK, Yoon OB, et al. The water-soluble fraction of bee venom produces antinociceptive and antiinflammatory effects on rheumatoid arthritis in rats. Life Sci. 2002; 71:191-204. https://doi.org/10.1016/S0024-3205(02)01617-X
  52. Yoon SY, Roh DH, Kwon YB, Kim HW, Seo HS, Han HJ, et al. Acupoint stimulation with diluted bee venom (apipuncture) potentiates the analgesic effect of intrathecal clonidine in the rodent formalin test and in a neuropathic pain model. J Pain. 2009; 10:253-63. https://doi.org/10.1016/j.jpain.2008.09.002
  53. Sun S, Chen WL, Wang PF, Zhao ZQ, Zhang YQ. Disruption of glial function enhances electroacupuncture analgesia in arthritic rats. Exp Neurol. 2006; 198:294-302 https://doi.org/10.1016/j.expneurol.2005.11.011
  54. Wong BJ, Crumley RL. Nerve wound healing. An overview. Otolaryngol Clin North Am. 1995; 28:881-95.
  55. Moir MS, Wang MZ, To M, Lum J, Terris DJ. Delayed repair of transected nerves: effect of brain-derived neurotrophic factor. Arch Otolaryngol Head Neck Surg. 2000; 126:501-5.
  56. Byun YH, Lee MH, Kim SS, Kim H, Chang HK, Lee TH, et al. Treadmill running promotes functional recovery and decreases brain-derived neurotrophic factor mRNA expression following sciatic crushed nerve injury in rats. J Sports Med Phys Fitness. 2005; 45:222-8.
  57. Meyer M, Matsuoka I, Wetmore C, Olson L, Thoenen H. Enhanced synthesis of brain-derived neurotrophic factor in the lesioned peripheral nerve: different mechanisms are responsible for the regulation of BDNF and NGF mRNA. J Cell Biol. 1992; 119:45-54. https://doi.org/10.1083/jcb.119.1.45
  58. Funakoshi H, Frisén J, Barbany G, Timmusk T, Zachrisson O, Verge VM, et al. Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. J Cell Biol. 1993; 123:455-65. https://doi.org/10.1083/jcb.123.2.455
  59. Novikova L, Novikov L, Kellerth JO. Effects of neurotransplants and BDNF on the survival and regeneration of injured adult spinal motoneurons. Eur J Neurosci. 1997; 9:2774-7. https://doi.org/10.1111/j.1460-9568.1997.tb01706.x
  60. Zhang JY, Luo XG, Xian CJ, Liu ZH, Zhou XF. Endogenous BDNF is required for myelination and regeneration of injured sciatic nerve in rodents. Eur J Neurosci. 2000; 12:4171-80.
  61. Gold BG, Storm-Dickerson T, Austin DR. Regulation of the transcription factor c-JUN by nerve growth factor in adult sensory neurons. Neurosci Lett. 1993; 154(1-2):129-33.
  62. Gold BG. Axonal regeneration of sensory nerves is delayed by continuous intrathecal infusion of nerve growth factor. Neuroscience. 1997; 76(4): 1153-8. https://doi.org/10.1016/S0306-4522(96)00416-2
  63. Mohiuddin L, Delcroix JD, Fernyhough P, Tomlinson DR. Focally administered nerve growth factor suppresses molecular regenerative responses of axotomized peripheral afferents in rats. Neuroscience. 1999; 91(1):265-71. https://doi.org/10.1016/S0306-4522(98)00582-X
  64. Hirata A, Masaki T, Motoyoshi K, Kamakura K. Intrathecal administration of nerve growth factor delays GAP 43 expression and early phase regeneration of adult rat peripheral nerve. Brain Res. 2002; 944(1-2):146-56.
  65. Bae JH, Lee BK, Kim SS. The effect of needle TENS to nerve growth factor (NGF) revelation after damage of the peripheral nerve of a white rat. Korean J. Life Science. 2003; 13(6):950-7. https://doi.org/10.5352/JLS.2003.13.6.950
  66. Dayas CV, Buller KM, Crane JW, Xu Y, Day TA. Stressor categorization: acute physical and psychological stressors elicit distinctive recruitment patterns in the amygdala and in medullary noradrenergic cell groups. Euro J Neurosci. 2001; 14:1143-52. https://doi.org/10.1046/j.0953-816x.2001.01733.x
  67. Engblom D, Ericsson-Dahlstrand ME, Blomqvist A. Activation of prostanoid EP3 and EP4 receptor mRNA-expressing neurons in the rat parabrachial nucleus by intravenous injection of bacterial wall lipopolysaccharide. J Compara Neuro. 2001; 440:378-86. https://doi.org/10.1002/cne.1391
  68. Birklein F. Mechanisms of neuropathic pain and their importance in Fabry disease. Acta Paediatr Suppl. 2002; 91:34-7.
  69. Rassnick S, Hoffman GE, Rabin BS, Sved AF. Injection of corticotropin-releasing hormone into the locus coeruleus or foot shock increases neuronal Fos expression. Neuroscience. 1998; 85:259-68. https://doi.org/10.1016/S0306-4522(97)00574-5
  70. Passerin AM, Cano G, Rabin BS, Delano BA, Napier JL, Sved AF. Role of locus coeruleus in foot shock-evoked Fos expression in rat brain. Neuroscience. 2000; 101:1071-82. https://doi.org/10.1016/S0306-4522(00)00372-9
  71. De Medeiros MA, Canteras NS, Suchecki D, Mello LE. Analgesia and c-Fos expression in the periaqueductal gray induced by electroacupuncture at the Zusanli point in rats. Brain Res. 2003; 973:196-204. https://doi.org/10.1016/S0006-8993(03)02479-X
  72. Hattori Y, Watanabe M, Iwabe T, Tanaka E, Nishi M, Aoyama J, et al. Administration of MK-801 decreases c-Fos expression in the trigeminal sensory nuclear complex but increases it in the midbrain during experimental movement of rat molars. Brain Res. 2004; 1021:183-91. https://doi.org/10.1016/j.brainres.2004.06.048
  73. Minoru N, Ozaki S, Narita M, Ise Y, Yajima YI, Suzuki T. Change in the expression of c-Fos in the rat brain following sciatic nerve ligation. Neurosci. Lett. 2003; 352:231-3. https://doi.org/10.1016/j.neulet.2003.08.052
  74. Son DJ, Lee JW, Lee YH, Song HS, Lee CK, Hong JT. Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol Ther. 2007; 115:246-70. https://doi.org/10.1016/j.pharmthera.2007.04.004
  75. Wu SX, Wang W, Wang YY, Ni TS, Li YQ, Yew DT. c-Fos antisense oligodeoxynucleotide decreases subcutaneous bee venom injectioninduced nociceptive behavior and Fos expression in the rat. Neurosignals. 2002; 11: 224-30. https://doi.org/10.1159/000065430