Summary
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.
Similar content being viewed by others
References
Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol, 2006, 80(2):53–83
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):447–459
Nickel FT, Seifert F, Lanz S, et al. Mechanisms of neuropathic pain. Eur Neuropsychopharmacol, 2012, 22(2): 81–91
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):164–172
Stein C, Clark JD, Oh U, et al. Peripheral mechanisms of pain and analgesia. Brain Res Rev, 2009, 60(1):90–113
Zhang Q, Tan Y. Nerve growth factor augments neuronal responsiveness to noradrenaline in cultured dorsal root ganglion neurons of rats. Neuroscience, 2011, 193:72–79
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):316–321
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):106–112
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):319–330
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):636–641
Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain, 1988, 33(1):87–107
Eddy NB, Leimbach D. Synthetic analgesics. II. Dithienybutenyl- and dithienybutylamines. J Pharmacol Exp Ther, 1953, 107(3):385–393
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): 533–542
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):696–699
Kukkar A, Bali A, Singh N, et al. Implications and mechanism of action of gabapentin in neuropathic pain. Arch Pharm Res, 2013, 36(3):237–251
Chung JM, Chung K. Importance of hyperexcitability of DRG neurons in neuropathic pain. Pain Pract, 2002, 2(2):87–97
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):2226–2233
Tan Y, Sun L, Zhang Q. Noradrenaline enhances ATP P2X3 receptor expression in dorsal root ganglion neurons of rats. Neuroscience, 2011, 176:32–38
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, 396
Dawson LF, Phillips JK, Finch PM, et al. Expression of α1-adrenoceptors on peripheral nociceptive neurons. Neuroscience, 2011, 175:300–314
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):968–976
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):21–24
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):108–111
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):2568–2576
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):195–206
Abdulla FA, Smith PA. Ectopic alpha2-adrenoceptors couple to N-type Ca2+ channels in axotomized rat sensory neurons. J Neurosci, 1997, 17(5):1633–1641
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): 189–197
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):202–205
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):5928–5937
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):386–394
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):45–61
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): 1760–1767
Gotoh Y, Andoh T, Kuraishi Y. Noradrenergic regulation of itch transmission in the spinal cord mediated by α-adrenoceptors. Neuropharmacology, 2011, 61(4): 825–831
Zhang Q, Tan Y. Nerve growth factor augments neuronal responsiveness to noradrenaline in cultured dorsal root ganglion neurons of rats. Neuroscience, 2011, 193:72–79
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, 252:512–525
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): 219–222
Author information
Authors and Affiliations
Corresponding author
Additional information
This project was supported by grants from the National Natural Science Foundation of China (No. 30160026) and the Youth Science and Technology Innovation Special Foundation of Xinjiang Production and Construction Corps, China (No. 2010JC33).
Rights and permissions
About this article
Cite this article
Cheng, Hj., Ma, Kt., Li, L. et al. Differential expression of alpha-adrenoceptor subtypes in rat dorsal root ganglion after chronic constriction injury. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 322–329 (2014). https://doi.org/10.1007/s11596-014-1277-1
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-014-1277-1