Differential expression of alpha-adrenoceptor subtypes in rat dorsal root ganglion after chronic constriction injury

  • Hong-ju Cheng (成洪聚)
  • Ke-tao Ma (马克涛)
  • Li Li (李 丽)
  • Lei Zhao (赵 磊)
  • Yang Wang (王 洋)
  • Jun-qiang Si (司军强)


mRNAs of alpha-adrenoceptor (α-AR) subtypes are found in neurons in dorsal root ganglion (DRG) and change after peripheral nerve injury. In this study, the distribution of α-AR subtype proteins was studied in L5 DRG of normal rats and rats with chronic constriction injury of sciatic nerve (CCI). Using immunofluorescence technique, it was found that α1A-, α1B-, and α2A-AR proteins were expressed in large, medium, and small size neurons in normal DRG, and significantly increased in all size neurons 14 days after CCI. α1D- and α2C-AR was also expressed in all size neurons in normal DRG. However, α1D-AR was significantly increased and α2C-AR was decreased in small size neurons 14 days post CCI. α2B-AR neurons were not detectable in normal and CCI DRG. Co-expression of α1A- and α2A-AR in the same neuron was observed in normal DRG and increased post CCI. Collectively, these results indicated that there is distinct distribution of α-AR subtypes in DRG neurons, and the distribution and levels of expression of α-AR subtypes change differently after CCI. The up-regulation of α-AR subtypes in DRG neurons may play an important role in the process of generating and transmitting neuropathic pain.

Key words

alpha-adrenoceptor chronic constriction injury dorsal root ganglion neuropathic pain noradrenaline 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol, 2006, 80(2):53–83PubMedCrossRefGoogle Scholar
  2. 2.
    Xie W, Strong JA, Zhang JM. Increased excitability and spontaneous activity of rat sensory neurons following in vitro stimulation of sympathetic fiber sprouts in the isolated dorsal root ganglion. Pain, 2010, 151(2):447–459PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Nickel FT, Seifert F, Lanz S, et al. Mechanisms of neuropathic pain. Eur Neuropsychopharmacol, 2012, 22(2): 81–91PubMedCrossRefGoogle Scholar
  4. 4.
    Xie J, Ho Lee Y, Wang C, et al. Differential expression of alpha1-adrenoceptor subtype mRNAs in the dorsal root ganglion after spinal nerve ligation. Brain Res Mol Brain Res, 2001, 93(2):164–172PubMedCrossRefGoogle Scholar
  5. 5.
    Stein C, Clark JD, Oh U, et al. Peripheral mechanisms of pain and analgesia. Brain Res Rev, 2009, 60(1):90–113PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Zhang Q, Tan Y. Nerve growth factor augments neuronal responsiveness to noradrenaline in cultured dorsal root ganglion neurons of rats. Neuroscience, 2011, 193:72–79PubMedCrossRefGoogle Scholar
  7. 7.
    Nicholson R, Dixon AK, Spanswick D, et al. Noradrenergic receptor mRNA expression in adult rat superficial dorsal horn and dorsal root ganglion neurons. Neurosci Lett, 2005, 380(3):316–321PubMedCrossRefGoogle Scholar
  8. 8.
    Maruo K, Yamamoto H, Yamamoto S, et al. Modulation of P2X receptors via adrenergic pathways in rat dorsal root ganglion neurons after sciatic never injury. Pain, 2006, 120(1–2):106–112PubMedCrossRefGoogle Scholar
  9. 9.
    Shi TS, Winzer-Serhan U, Leslie F, et al. Distribution and regulation of alpha (2)-adrenoceptors in rat dorsal root ganglia. Pain, 2000, 84(2–3):319–330PubMedCrossRefGoogle Scholar
  10. 10.
    Duflo F, Li X, Bantel C, et al. Peripheral nerve injury alters the alpha2 adrenoceptor subtype activated by clonidine for analgesia. Anesthesiol, 2002, 97(3):636–641CrossRefGoogle Scholar
  11. 11.
    Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain, 1988, 33(1):87–107PubMedCrossRefGoogle Scholar
  12. 12.
    Eddy NB, Leimbach D. Synthetic analgesics. II. Dithienybutenyl- and dithienybutylamines. J Pharmacol Exp Ther, 1953, 107(3):385–393PubMedGoogle Scholar
  13. 13.
    Birder LA, Perl ER. Expression of alpha2-adrenergic receptors in rat primary afferent neurons after peripheral nerve injury or inflammation. J Physiol, 1999, 515 (Pt2): 533–542CrossRefGoogle Scholar
  14. 14.
    Liu Y, Yao S, Song W, et al. Effects of intrathecally administerd NaV1.8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion. J Huazhong Univ Sci Technolog Med Sci, 2005, 25(6):696–699PubMedCrossRefGoogle Scholar
  15. 15.
    Kukkar A, Bali A, Singh N, et al. Implications and mechanism of action of gabapentin in neuropathic pain. Arch Pharm Res, 2013, 36(3):237–251PubMedCrossRefGoogle Scholar
  16. 16.
    Chung JM, Chung K. Importance of hyperexcitability of DRG neurons in neuropathic pain. Pain Pract, 2002, 2(2):87–97PubMedCrossRefGoogle Scholar
  17. 17.
    Lee DH, Liu XZ, Kim HT, et al. Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats. J Neurophysiol, 1999, 81(5):2226–2233PubMedGoogle Scholar
  18. 18.
    Tan Y, Sun L, Zhang Q. Noradrenaline enhances ATP P2X3 receptor expression in dorsal root ganglion neurons of rats. Neuroscience, 2011, 176:32–38PubMedCrossRefGoogle Scholar
  19. 19.
    Bai X, Jiang L, Xiang Z. Localization of P2X7 receptor immunoreactivity in the dorsal root ganglia of guinea pig. J Huazhong Univ Sci Technolog Med Sci, 2005, 25(4): 371–374, 396PubMedCrossRefGoogle Scholar
  20. 20.
    Dawson LF, Phillips JK, Finch PM, et al. Expression of α1-adrenoceptors on peripheral nociceptive neurons. Neuroscience, 2011, 175:300–314PubMedCrossRefGoogle Scholar
  21. 21.
    Ongioco RR, Richardson CD, Rudner XL, et al. Alpha2-adrenergic receptors in human dorsal root ganglia: predominance of alpha2b and alpha2c subtype mRNAs. Anesthesiol, 2000, 92(4):968–976CrossRefGoogle Scholar
  22. 22.
    Banik RK, Sato J, Yajima H, et al. Differences between the Lewis and Sprague-Dawley rats in chronic inflammation induced norepinephrine sensitivity of cutaneous C-fiber nociceptors. Neurosci Lett, 2001, 299(1–2):21–24PubMedCrossRefGoogle Scholar
  23. 23.
    Chen W, Yang J, Shi J, et al. Effects of electroacupuncture on the pain threshold and the NMDA R1 mRNA in DRG on neuropathic pain rats. J Huazhong Univ Sci Technolog Med Sci, 2003, 23(2):108–111PubMedCrossRefGoogle Scholar
  24. 24.
    Tanimoto K, Takebayashi T, Kobayashi T, et al. Does norepinephrine influence pain behavior mediated by dorsal root ganglia?: a pilot study. Clin Orthop Relat Res, 2011, 469(9):2568–2576PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Honma Y, Yamakage M, Ninomiya T. Effects of adrenergic stimulus on the activities of Ca2+ and K+ channels of dorsal root ganglion neurons in a neuropathic pain model. Brain Res, 1999, 832(1–2):195–206PubMedCrossRefGoogle Scholar
  26. 26.
    Abdulla FA, Smith PA. Ectopic alpha2-adrenoceptors couple to N-type Ca2+ channels in axotomized rat sensory neurons. J Neurosci, 1997, 17(5):1633–1641PubMedGoogle Scholar
  27. 27.
    Eisenach JC, Zhang Y, Duflo F. alpha2-adrenoceptors inhibit the intracellular Ca2+ response to electrical stimulation in normal and injured sensory neurons, with increased inhibition of calcitonin gene-related peptide expressing neurons after injury. Neuroscience, 2005, 131(1): 189–197PubMedCrossRefGoogle Scholar
  28. 28.
    Gong H, Liu Q, Yang X, et al. Effects of selective alpha 2-adrenoreceptor stimulation on capsaicin-evoked substance P release from primary cultured dorsal root ganglion neurons. Pharmazie, 2010, 65(3):202–205PubMedGoogle Scholar
  29. 29.
    Stone LS, Broberger C, Vulchanova L, et al. Differential distribution of alpha2A and alpha2C adrenergic receptor immunoreactivity in the rat spinal cord. J Neurosci, 1998, 18(15):5928–5937PubMedGoogle Scholar
  30. 30.
    Ma W, Zhang Y, Bantel C, et al. Medium and large injured dorsal root ganglion cells increase TRPV-1, accompanied by increased alpha2C-adrenoceptor co-expression and functional inhibition by clonidine. Pain, 2005, 113(3):386–394PubMedCrossRefGoogle Scholar
  31. 31.
    Bester H, Beggs S, Woolf CJ. Changes in tactile stimuli-induced behavior and c-Fos expression in the superficial dorsal horn and in parabrachial nuclei after sciatic nerve crush. J Comp Neurol, 2000, 428(1):45–61PubMedCrossRefGoogle Scholar
  32. 32.
    Tamagaki S, Suzuki T, Hagihira S, et al. Systemic daily morphine enhances the analgesic effect of intrathecal dexmedetomidine via up-regulation of alpha 2 adrenergic receptor subtypes A, B, and C in dorsal root ganglion and dorsal Horn. J Pharm Pharmacol, 2010, 62(12): 1760–1767PubMedCrossRefGoogle Scholar
  33. 33.
    Gotoh Y, Andoh T, Kuraishi Y. Noradrenergic regulation of itch transmission in the spinal cord mediated by α-adrenoceptors. Neuropharmacology, 2011, 61(4): 825–831PubMedCrossRefGoogle Scholar
  34. 34.
    Zhang Q, Tan Y. Nerve growth factor augments neuronal responsiveness to noradrenaline in cultured dorsal root ganglion neurons of rats. Neuroscience, 2011, 193:72–79PubMedCrossRefGoogle Scholar
  35. 35.
    Webber CA, Salame J, Luu GL, et al. Nerve growth factor acts through the TrkA receptor to protect sensory neurons from the damaging effects of the HIV-1 viral protein, Vpr. Neuroscience, 2013, 252:512–525PubMedCrossRefGoogle Scholar
  36. 36.
    Wan L, Luo A, Yu H, et al. Effect of touch-stimulus on the expression of C-fos and TrkA in spinal cord following chronic constriction injury of the sciatic nerve in rats. J Huazhong Univ Sci Technolog Med Sci, 2005, 25(2): 219–222PubMedCrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Hong-ju Cheng (成洪聚)
    • 1
  • Ke-tao Ma (马克涛)
    • 2
  • Li Li (李 丽)
    • 2
  • Lei Zhao (赵 磊)
    • 2
  • Yang Wang (王 洋)
    • 1
  • Jun-qiang Si (司军强)
    • 1
    • 2
    • 3
  1. 1.Department of PhysiologyBasic Medical School of Wuhan UniversityWuhanChina
  2. 2.Electrophysiological Laboratory, Laboratory of Xinjiang Endemic and Ethnic DiseasesMedical College of Shihezi UniversityShiheziChina
  3. 3.Department of Neurobiology, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations