Neural Plasticity

Neural Plasticity / 2013 / Article
Special Issue

Neurological Disorders Related Neuronal Network Impairment: Function and Mechanism

View this Special Issue

Review Article | Open Access

Volume 2013 |Article ID 424651 |

Ming Zhang, Wenjuan Han, Sanjue Hu, Hui Xu, "Methylcobalamin: A Potential Vitamin of Pain Killer", Neural Plasticity, vol. 2013, Article ID 424651, 6 pages, 2013.

Methylcobalamin: A Potential Vitamin of Pain Killer

Academic Editor: Sheng Tian Li
Received19 Sep 2013
Revised06 Nov 2013
Accepted12 Nov 2013
Published26 Dec 2013


Methylcobalamin (MeCbl), the activated form of vitamin B12, has been used to treat some nutritional diseases and other diseases in clinic, such as Alzheimer’s disease and rheumatoid arthritis. As an auxiliary agent, it exerts neuronal protection by promoting regeneration of injured nerves and antagonizing glutamate-induced neurotoxicity. Recently several lines of evidence demonstrated that MeCbl may have potential analgesic effects in experimental and clinical studies. For example, MeCbl alleviated pain behaviors in diabetic neuropathy, low back pain and neuralgia. MeCbl improved nerve conduction, promoted the regeneration of injured nerves, and inhibited ectopic spontaneous discharges of injured primary sensory neurons. This review aims to summarize the analgesic effect and mechanisms of MeCbl at the present.

1. Introduction

Vitamin B12 had been usually treated as sport nutrition, and used to keep old people from getting anemic in past years. Vitamin B12 was regarded as painkilling vitamin in some countries from 1950. Recently studies have shown that vitamin B12 played a key role in the normal functioning of the brain and nervous system and the formation of blood. Vitamin B12 is normally involved in several metabolisms such as DNA synthesis and regulation, fatty acid synthesis, and energy production. Vitamin B12 has some analogs including cyanocobalamin (CNCbl), methylcobalamin (MeCbl), hydroxocobalamin (OHCbl), and adenosylcobalamin (AdoCbl). In mammalian cells, CNCbl and OHCbl are inactive forms and AdoCbl acts as a coenzyme of methylmalonyl Co-A mutase in mitochondria. However, vitamin B12 was not used directly in human body, and it should be translated into activating forms such as MeCbl or AdoCbl. MeCbl differs from vitamin B12 in that the cyanide is replaced by a methyl group (Figure 1) [1]. It is a coenzyme of methionine synthase, which is required for the formation of methionine from homocysteine in the methylation cycle which involves methylation of DNA or proteins [25]. Compared with other analogs, MeCbl is the most effective one in being uptaken by subcellular organelles of neurons. Therefore, MeCbl may provide better treatments for nervous disorders through effective systemic or local delivery.

As an auxiliary agent, MeCbl has been always used to treat many diseases, such as B12 deficiency and Alzheimer’s disease syndromes [6, 7]. L-methylfolate, MeCbl, and N-acetylcysteine improved memory, emotional functions, and communication with other people among Alzheimer’s patients [7, 8]. MeCbl also has neuronal protection including promoting injured nerve and axonal regeneration [9, 10] and confronting against glutamate-induced neurotoxicity [9, 11]. In addition, MeCbl improved nerve conduction in either patients of diabetic neuropathy [1214] or streptozotocin-diabetic rats [15] and experimental acrylamide neuropathy [16]. MeCbl also improved visual function [17], rheumatoid arthritis [18], Bell’s palsy, and sleep-wake rhythm disorder [19, 20]. Recently, MeCbl has been demonstrated to have potential analgesic effects on neuropathic pain in experimental and clinical studies.

2. The Analgesic Effect of MeCbl

MeCbl is one active form of vitamin B12 which can directly participate in homocysteine metabolism. More and more researches showed that MeCbl has beneficial effects on clinical and experimental peripheral neuropathy.

2.1. Diabetic Peripheral Neuropathic Pain

Clinical symptoms in legs, such as paresthesia, burning pains, and spontaneous pain, were ameliorated by MeCbl [21, 22] (Table 1). The effects of single use of MeCbl or combined use with other drugs were reviewed in diabetic neuropathy pain [12, 23] (Table 1). Clinical evidence proved that MeCbl had the capacity to inhibit the neuropathic pain associated with diabetic neuropathy.

Effects of MeCbl Indices Measures of interventionReference

Alleviation of neuropathic pain symptoms;
improved nerve conduction velocity
Pain scale scores of patients; measure of nerve conduction velocityOral administration of MeCbl for 3 months Devathasan et al. [12]

Improved nerve conduction velocityMeasure of nerve conduction velocityIntravenous administration of MeCblIshihara et al. [14]

Improved the symptoms of paresthesia, burning pains, and heaviness;
no effect on nerve conduction velocity
Pain symptoms; measure of nerve conduction velocityRepeated intrathecal injection of MeCbl at a high dose of 2.5 mg/10 mLIde et al. [21]

Relieved spontaneous pain by 73% Likert-type pain intensity scale; Patients’ Global Impression of Change (PGIC) scaleIntramuscular injection of MeCbl for four weeks followed by oral administration of MeCbl for additional eight weeksLi [22]

Relieved pain and paresthesia;
improved motor and sensory nerve conduction velocity
Neurolgical disability score for the grades of pain and paresthesia Intravenous injection of MeCbl for 6 weeksKuwabara et al. [13]

Reduced pain scores and good toleranceVisual analog scale and chemical safety Oral administration of immediate-release methylcobalamin and sustained-release pregabalin for 2 weeks. Dongre and Swami [23]

The intensity of the pain is variable and may be described as a hot, burning, cold, aching, or itching sensation with, at times, increased skin sensitivity. In clinics, it is still a challenge to treat diabetic neuropathic pain. Carbamazepine and dolantin were not able to relieve these symptoms. Similarly, therapeutic effects of aldose reductase inhibitors and nimodipine were not encouraging in clinic as much as basic studies showed. Fortunately, MeCbl may bring a glimmer of hope to treat diabetic neuropathic pain.

2.2. Low Back Pain

Between 70 and 80% adults have experienced low back pain at some times in their life [24]. Back pain is one of the most common health complaints. But the causes are extensive, cancer, infection, inflammatory disorders, structural disorders of the spine itself, and disk herniation, are somewhat more common, and together account for back pain. It is supposed that the MeCbl is becoming a decent choice for the therapy to the chronic low back pain. Neurogenic claudication distance was improved significantly after the application of MeCbl [25] (Table 2). However Waikakul’s research demonstrated that MeCbl was not good for pain on lumbar spinal stenosis [25]. In a trial, the analgesic effect of MeCbl has been investigated in nonspecific low back pain patients with intramuscular injection [26] (Table 2). The inconsistent effect of MeCbl might be due to different causes of lumbar spinal stenosis and nonspecific low back pain. Further studies are needed to determine the effect of MeCbl on low back pain.

Effects of MeCbl Indices Measures of intervention Reference

Relieved spontaneous pain, allodynia, and paresthesia.Pain symptoms of patients with neck painOral administration of MeCbl for 4 weeksHanai et al. [29]

Amelioration of neurogenic claudication distance; no effect on pain improvement and neurological signsPain symptoms; measure the neurogenic claudication distance of patients with degenerative lumbar spinal stenosisOral administration of MeCbl as an adjuvant medication for 6 monthsW. Waikakul and S. Waikakul [25]

Reduced pain Oswestry disability index questionnaire (ODI) and visual analogue scale (VAS) pain score of patients with nonspecific low back painIntramuscular injection of MeCbl for 2 weeksChiu et al. [26]

2.3. Neck Pain

Chronic neck pain is becoming a common problem in the adult population, for the prevalence of 30%–50% in 12 months [27, 28]. It was shown that spontaneous pain, allodynia, and paresthesia of patients with neck pain were improved significantly in the MeCbl group, and with the increase of treatment time of MeCbl, the analgesic effect was more obvious [29] (Table 2).

2.4. Neuralgia
2.4.1. Subacute Herpetic Neuralgia

The treatment of MeCbl significantly reduced continuous pain, paroxysmal pain, and allodynia in the subacute herpetic neuralgia (SHN) patients [30] (Table 3). Thus, MeCbl may be an alternative candidate for treating SHN.

Effects of MeCbl Indices Measures of intervention Reference

Reduced or eliminated pain symptomsPain scales in patients with trigeminal neuralgiaIntravenous injection of MeCbl at a single dose of 0.5 mg Teramoto [32]

Relieved overall pain, continuous spontaneous pain, paroxysmal pain, and allodyniaLikert-type pain intensity scale; Patients’ Global Impression of Change (PGIC) scaleLocal subcutaneous injection of MeCbl for 4 weeksXu et al. [30]

Lowered pain intensities; improved pain relief; reduced pain interference with quality of lifeNumerical pain scale and brief pain inventory of glossopharyngeal neuralgiaOral administration of gabapentin, tramadol, and MeCbl (0.5 mg) Singh et al. [31]

2.4.2. Glossopharyngeal Neuralgia

Glossopharyngeal neuralgia (GPN) is a common facial neuralgia in the pain clinics. It was reported that the numerical pain scales were decreased substantially with the treatment of MeCbl combined with gabapentin and tramadol in GPN patients [31] (Table 3). And degree of interference in quality of life including mood, interpersonal relationship, and emotion was improved earlier [31].

2.4.3. Trigeminal Neuralgia

The pain of trigeminal neuralgia (TN) can be described as agonizing, paroxysmal and lancinating which may be activated by small activities such as chewing, speaking, and swallowing. A clinical trial proved that the pain of TN patients was alleviated greatly in the MeCbl group, and no recurrence of TN in pain symptoms was closed to 64% [32] (Table 3).

2.5. Neuropathic Pain of Animal Models

The coapplication of MeCbl and pioglitazone dramatically decreased allodynia and hyperalgesia in diabetic rats [33]. And the combined application of MeCbl and vitamin E alleviated thermal hyperalgesia in sciatic nerve crush injured rats [34]. Our recent work observed that tactile allodynia was markedly alleviated following a chronic treatment of MeCbl injection in chronic compression of dorsal root ganglion (CCD) rats (Figure 2).

3. Mechanisms Underlying the Analgesic of MeCbl

For many years, the B12 group of vitamins had been used to treat pain. In some countries, vitamin B12 was categorised as an analgesic drug. It was suggested that vitamin B12 may increase availability and effectiveness of noradrenaline and 5-hydroxytryptamine in the descending inhibitory nociceptive system [35]. MeCbl exerted therapeutic effects on neuropathic pain in diabetics, possibly through its neurosynthesis and neuroprotective actions [13, 36]. But the analgesic mechanisms of MeCbl remained elusive till now.

3.1. Improving Nerve Conduction Velocity

Previous studies showed that high doses of MeCbl improved nerve conduction in either patients with diabetic neuropathy [1214], streptozotocin-diabetic rats [15], or experimental acrylamide neuropathy [16]. Morphological and histological evidence confirmed that a long-term administration of MeCbl promoted the synthesis and regeneration of myelin [37]. These morphological and histological recoveries of myelin may result in improving nerve conduction velocity and neuronal function in peripheral neuropathy.

3.2. Promoting the Regeneration of Injured Nerves

MeCbl advanced the incorporation of radioactive leucine into the protein fraction of the crushed sciatic nerve in vivo. As a result, the activity abilities of injured nerve were recovered [38]. In this study, the most terminals were degenerated in the mutant mouse, but the sprouts were more frequently observed in the MeCbl treatment group [39]. MeCbl had the ability to promote the injured nerves regeneration. In the experimental acrylamide neuropathy and sciatic nerve injury models, the number of regenerations of motor fibers showed significant increase with high-dose methylcobalamin [16]. And the combined use of L-methylfolate, MeCbl, and pyridoxal 5′-phosphate improved the calf muscle surface neural density [40].

3.3. Inhibiting Ectopic Spontaneous Discharge

Ectopic spontaneous discharges are likely to initiate spontaneous pain, hyperalgesia, and allodynia [4145]. It was reported that MeCbl suppressed the ectopic firing induced by chemical materials in the dog dorsal root [46]. Our recent work demonstrated that MeCbl markedly inhibited the ectopic spontaneous discharges of dorsal root ganglion neurons in CCD rats (Figure 3). Our results suggested that MeCbl exhibited its anti-allodynic effect by inhibiting peripheral pain signals.

4. Conclusions

MeCbl or its combined use with other agents has the potential analgesic effect in specific patients and animal models, for example, nonspecific low back pain; neck pain; diabetic neuropathic pain, subacute herpetic neuralgia, glossopharyngeal neuralgia, and trigeminal neuralgia. However, its mechanisms underlying the analgesic effect were poorly understood. On the basis of recent work, the possible mechanisms can be considered as follows. (1) MeCbl improved nerve conduction velocity; (2) MeCbl promoted injured nerve regeneration, recovering the neuromuscular functions in peripheral hyperalgesia and allodynia; and (3) MeCbl inhibited the ectopic spontaneous discharges from peripheral primary sensory neurons in neuropathic pain states. As a vitamin, MeCbl may be a potential candidate for treating peripheral neuropathy with good safety.


This work was supported by Grants from the National Natural Science Foundation of China (nos. 30870830 and 31371120 to Dr. Hui Xu) and the Ministry of Education Foundation for returned overseas students (HG3503 to Dr. Hui Xu).


  1. L. R. McDowell, Vitamins in Animal and Human Nutrition, John Wiley & Sons, 2008.
  2. R. Banerjee and S. W. Ragsdale, “The many faces of vitamin B12: catalysis by cobalamin-dependent enzymes,” Annual Review of Biochemistry, vol. 72, pp. 209–247, 2003. View at: Publisher Site | Google Scholar
  3. S. K. Ghosh, N. Rawal, S. K. Syed, W. K. Paik, and S. D. Kim, “Enzymic methylation of myelin basic protein in myelin,” Biochemical Journal, vol. 275, part 2, pp. 381–387, 1991. View at: Google Scholar
  4. A. Pfohl-Leszkowicz, G. Keith, and G. Dirheimer, “Effect of cobalamin derivatives on in vitro enzymatic DNA methylation: methylcobalamin can act as a methyl donor,” Biochemistry, vol. 30, no. 32, pp. 8045–8051, 1991. View at: Google Scholar
  5. J. I. Toohey, “Vitamin B12 and methionine synthesis: a critical review. Is nature's most beautiful cofactor misunderstood?” BioFactors, vol. 26, no. 1, pp. 45–57, 2006. View at: Publisher Site | Google Scholar
  6. Y. Takahashi, S. Usui, and Y. Honda, “Effect of vitamin B12 (mecobalamin) on the circadian rhythm of rat behavior,” Clinical Neuropharmacology, vol. 15, supplement 1, part A, pp. 46A–47A, 1992. View at: Google Scholar
  7. A. McCaddon and P. R. Hudson, “L-methylfolate, methylcobalamin, and N-acetylcysteine in the treatment of Alzheimer's disease-related cognitive decline,” CNS Spectrums, vol. 15, supplement 1, no. 1, pp. 2–6, 2010. View at: Google Scholar
  8. T. Ikeda, K. Yamamoto, K. Takahashi et al., “Treatment of Alzheimer-type dementia with intravenous mecobalamin,” Clinical Therapeutics, vol. 14, no. 3, pp. 426–437, 1992. View at: Google Scholar
  9. M. Kikuchi, S. Kashii, Y. Honda, Y. Tamura, K. Kaneda, and A. Akaike, “Protective effects of methylcobalamin, a vitamin B12 analog, against glutamate-induced neurotoxicity in retinal cell culture,” Investigative Ophthalmology and Visual Science, vol. 38, no. 5, pp. 848–854, 1997. View at: Google Scholar
  10. X. Kong, X. Sun, and J. Zhang, “The protective role of Mecobalamin following optic nerve crush in adult rats,” Yan Ke Xue Bao, vol. 20, no. 3, pp. 171–177, 2004. View at: Google Scholar
  11. A. Akaike, Y. Tamura, Y. Sato, and T. Yokota, “Protective effects of a vitamin B12 analog, methylcobalamin, against glutamate cytotoxicity in cultured cortical neurons,” European Journal of Pharmacology, vol. 241, no. 1, pp. 1–6, 1993. View at: Publisher Site | Google Scholar
  12. G. Devathasan, W. L. Teo, and A. Mylvaganam, “Methylcobalamin in chronic diabetic neuropathy. A double-blind clinical and electrophysiological study,” Clinical Trials Journal, vol. 23, no. 2, pp. 130–140, 1986. View at: Google Scholar
  13. S. Kuwabara, R. Nakazawa, N. Azuma et al., “Intravenous methylcobalamin treatment for uremic and diabetic neuropathy in chronic hemodialysis patients,” Internal Medicine, vol. 38, no. 6, pp. 472–475, 1999. View at: Google Scholar
  14. H. Ishihara, M. Yoneda, W. Yamamoto et al., “Efficacy of intravenous administration of methycobalamin for diabetic peripheral neuropathy,” Med Consult N Remedies, vol. 29, no. 1, pp. 1720–1725, 1992. View at: Google Scholar
  15. M. Sonobe, H. Yasuda, I. Hatanaka et al., “Methylcobalamin improves nerve conduction in streptozotocin-diabetic rats without affecting sorbitol and myo-inositol contents of sciatic nerve,” Hormone and Metabolic Research, vol. 20, no. 11, pp. 717–718, 1988. View at: Google Scholar
  16. T. Watanabe, R. Kaji, N. Oka, W. Bara, and J. Kimura, “Ultra-high dose methylcobalamin promotes nerve regeneration in experimental acrylamide neuropathy,” Journal of the Neurological Sciences, vol. 122, no. 2, pp. 140–143, 1994. View at: Publisher Site | Google Scholar
  17. T. Iwasaki and S. Kurimoto, “Effect of methylcobalamin in accommodative dysfunction of eye by visual load,” Journal of UOEH, vol. 9, no. 2, pp. 127–132, 1987. View at: Google Scholar
  18. M. Yamashiki, A. Nishimura, and Y. Kosaka, “Effects of methylcobalamin (vitamin B12) on in vitro cytokine production of peripheral blood mononuclear cells,” Journal of Clinical and Laboratory Immunology, vol. 37, no. 4, pp. 173–182, 1992. View at: Google Scholar
  19. M. Ikeda, M. Asai, T. Moriya, M. Sagara, S. Inoué, and S. Shibata, “Methylcobalamin amplifies melatonin-induced circadian phase shifts by facilitation of melatonin synthesis in the rat pineal gland,” Brain Research, vol. 795, no. 1-2, pp. 98–104, 1998. View at: Publisher Site | Google Scholar
  20. K. Takahashi, M. Okawa, M. Matsumoto et al., “Double-blind test on the efficacy of methylcobalamin on sleep-wake rhythm disorders,” Psychiatry and Clinical Neurosciences, vol. 53, no. 2, pp. 211–213, 1999. View at: Publisher Site | Google Scholar
  21. H. Ide, S. Fujiya, Y. Asanuma, M. Tsuji, H. Sakai, and Y. Agishi, “Clinical usefulness of intrathecal injection of methylcobalamin in patients with diabetic neuropathy,” Clinical Therapeutics, vol. 9, no. 2, pp. 183–192, 1987. View at: Google Scholar
  22. G. Li, “Effect of mecobalamin on diabetic neuropathies. Beijing Methycobal Clinical Trial Collaborative Group,” Zhonghua Nei Ke Za Zhi, vol. 38, no. 1, pp. 14–17, 1999. View at: Google Scholar
  23. Y. U. Dongre and O. C. Swami, “Sustained-release pregabalin with methylcobalamin in neuropathic pain: an Indian real-life experience,” International Journal of General Medicine, vol. 6, pp. 413–417, 2013. View at: Google Scholar
  24. J. W. Frymoyer, “Back pain and sciatica,” The New England Journal of Medicine, vol. 318, no. 5, pp. 291–300, 1988. View at: Google Scholar
  25. W. Waikakul and S. Waikakul, “Methylcobalamin as an adjuvant medication in conservative treatment of lumbar spinal stenosis,” Journal of the Medical Association of Thailand, vol. 83, no. 8, pp. 825–831, 2000. View at: Google Scholar
  26. C. K. Chiu, T. H. Low, Y. S. Tey, V. A. Singh, and H. K. Shong, “The efficacy and safety of intramuscular injections of methylcobalamin in patients with chronic nonspecific low back pain: a randomised controlled trial,” Singapore Medical Journal, vol. 52, no. 12, pp. 868–873, 2011. View at: Google Scholar
  27. L. Manchikanti, E. E. Dunbar, B. W. Wargo, R. V. Shah, R. Derby, and S. P. Cohen, “Systematic review of cervical discography as a diagnostic test for chronic spinal pain,” Pain Physician, vol. 12, no. 2, pp. 305–321, 2009. View at: Google Scholar
  28. L. Manchikanti, S. Abdi, S. Atluri et al., “American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: part I—evidence assessment,” Pain Physician, vol. 15, no. 3, pp. S1–S65, 2012. View at: Google Scholar
  29. I. Y. Hanai, M. K'Yatsume et al., “Clinical study of methylcobalamin on cervicales,” Drug Therapy, vol. 13, no. 4, p. 29, 1980. View at: Google Scholar
  30. G. Xu, Z. W. Lv, Y. Feng, W. Z. Tang, and G. X. Xu, “A single-center randomized controlled trial of local methylcobalamin injection for subacute herpetic neuralgia,” Pain Medicine, vol. 14, no. 6, pp. 884–894, 2013. View at: Google Scholar
  31. P. M. Singh, M. Dehran, V. K. Mohan, A. Trikha, and M. Kaur, “Analgesic efficacy and safety of medical therapy alone vs combined medical therapy and extraoral glossopharyngeal nerve block in glossopharyngeal neuralgia,” Pain Medicine, vol. 14, pp. 93–102, 2013. View at: Google Scholar
  32. J. Teramoto, “Effects of Methylcobalamin on neuralgia,” Neurological Therapeutics, vol. 1, no. 2, p. 315, 1984. View at: Google Scholar
  33. A. S. Morani and S. L. Bodhankar, “Neuroprotecive effect of early treatment with pioglitasone and methylcobalamin in alloxan induced diabetes in rats,” Pharmacologyonline, vol. 3, pp. 282–293, 2007. View at: Google Scholar
  34. A. S. Morani and S. L. Bodhankar, “Early co-administration of vitamin E acetate and methylcobalamin improves thermal hyperalgesia and motor nerve conduction velocity following sciatic nerve crush injury in rats,” Pharmacological Reports, vol. 62, no. 2, pp. 405–409, 2010. View at: Google Scholar
  35. I. Jurna, “Analgesic and analgesia-potentiating action of B vitamins,” Schmerz, vol. 12, no. 2, pp. 136–141, 1998. View at: Publisher Site | Google Scholar
  36. Y. Sun, M. S. Lai, and C. J. Lu, “Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials,” Acta Neurologica Taiwanica, vol. 14, no. 2, pp. 48–54, 2005. View at: Google Scholar
  37. K. Okada, H. Tanaka, K. Temporin et al., “Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model,” Experimental Neurology, vol. 222, no. 2, pp. 191–203, 2010. View at: Publisher Site | Google Scholar
  38. K. Yamatsu, Y. Yamanishi, T. Kaneko, and I. Ohkawa, “Pharmacological studies on degeneration and regeneration of peripheral nerves. (II). Effects of methylcobalamin on mitosis of Schwann cells and incorporation of radio active leucine into protein fraction of crushed sciatic nerve in rats,” Folia Pharmacologica Japonica, vol. 72, no. 2, pp. 269–278, 1976 (Japanese). View at: Google Scholar
  39. K. Yamazaki, K. Oda, C. Endo, T. Kikuchi, and T. Wakabayashi, “Methylcobalamin (methyl-B12) promotes regeneration of motor nerve terminals degenerating in anterior gracile muscle of gracile axonal dystrophy (GAD) mutant mouse,” Neuroscience Letters, vol. 170, no. 1, pp. 195–197, 1994. View at: Publisher Site | Google Scholar
  40. A. M. Jacobs and D. Cheng, “Management of diabetic small-fiber neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5′-phosphate,” Reviews in Neurological Diseases, vol. 8, no. 1-2, pp. 39–47, 2011. View at: Publisher Site | Google Scholar
  41. W.-H. Xiao and G. J. Bennett, “Synthetic ω-conopeptides applied to the site of nerve injury suppress neuropathic pains in rats,” Journal of Pharmacology and Experimental Therapeutics, vol. 274, no. 2, pp. 666–672, 1995. View at: Google Scholar
  42. Y. W. Yoon, H. S. Na, and J. M. Chung, “Contributions of injured and intact afferents to neuropathic pain in an experimental rat model,” Pain, vol. 64, no. 1, pp. 27–36, 1996. View at: Publisher Site | Google Scholar
  43. Y. S. Lyu, S. K. Park, K. Chung, and J. M. Chung, “Low dose of tetrodotoxin reduces neuropathic pain behaviors in an animal model,” Brain Research, vol. 871, no. 1, pp. 98–103, 2000. View at: Publisher Site | Google Scholar
  44. J. Lai, M. S. Gold, C. S. Kim et al., “Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8,” Pain, vol. 95, no. 1-2, pp. 143–152, 2002. View at: Publisher Site | Google Scholar
  45. S. R. Chaplan, H.-Q. Guo, D. H. Lee et al., “Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain,” The Journal of Neuroscience, vol. 23, no. 4, pp. 1169–1178, 2003. View at: Google Scholar
  46. I. T. Atsuta Y, O. Sugawara, T. Muramoto, T. Watakabe, and Y. Takemitsu, “The study of generating and suppressive factors of ectopic firing in the lumbar dorsal root using an in vitro model,” Rinsho Seikei Geka, vol. 29, pp. 441–446, 1994. View at: Google Scholar

Copyright © 2013 Ming Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Related articles

No related content is available yet for this article.
 PDF Download Citation Citation
 Download other formatsMore
 Order printed copiesOrder

Related articles

No related content is available yet for this article.

Article of the Year Award: Outstanding research contributions of 2021, as selected by our Chief Editors. Read the winning articles.