The Journal of Physiological Sciences

, Volume 67, Issue 3, pp 431–438 | Cite as

Noradrenergic inhibition of spinal hyperexcitation elicited by cutaneous cold stimuli in rats with oxaliplatin-induced allodynia: electrophysiological and behavioral assessments

Short Communication


We investigated the spinal action of noradrenaline on cold-elicited hyperexcitation detected in dorsal horn neurons of rats with allodynia induced by an oxaliplatin (6 mg/kg, i.p.) injection. In vivo extracellular recordings from the spinal dorsal horn showed that wide dynamic range neurons responded to cutaneous acetone (10 μl) stimulation in normal rats, and cold-elicited firings in oxaliplatin-administered rats were increased with a longer duration, correlated with behavioral responses. These responses were significantly attenuated by spinal administration (50 μM) of noradrenaline or its agonists, clonidine (α2), phenylephrine (α1) and isoprenaline (β), in descending order of efficacy. Thus, the inhibitory effect of noradrenaline on spinal oxaliplatin-induced cold hyperexcitation is mediated mainly by activation of α2- and/or α1-adrenoceptors.


Noradrenaline Oxaliplatin Cold allodynia Spinal cord Wide dynamic range neurons In vivo extracellular recording 



We would like to thank Dr. Kazuhiko Seki and Ms. Ayumi Nakamura for their helpful advice on data analysis and technical support. This work was supported by grants from the programs Grants-in-Aid for Scientific Research (H.F.) from the Ministry of Education, Science, Sports and Culture of Japan, by a grant from the National Research Foundation of Korea (S.K.K) funded by the Korea Government (NRF-2013R1A1A1012403), and by a Grant (S.K.K.) from the Korea Institute of Oriental Medicine (C15012).

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.

Supplementary material

12576_2016_505_MOESM1_ESM.pdf (17 kb)
Supplementary Fig. 1. Firing rates of spinal WDR neurons during mechanical stimuli and behavioral signs of mechanical hypersensitivity. (A–C) Increased firings caused by light touch (brushing with camel hair) (A), press (pressing with the tip of brush) (B), and pinch (pinching with forceps) (C), were observed in oxaliplatin injected model (N = 20 for each group). ***p < 0.001, *p < 0.05, by unpaired t-test. (D–E) von Frey hair test showed that no change in mechanical sensitivity before and after vehicle control injection was observed (D), whereas mechanical hypersensitivity was developed following oxaliplatin injection (E). N = 7 for control group and N = 8 for oxaliplatin group. **p < 0.01, by paired t-test. (PDF 17 kb)
12576_2016_505_MOESM2_ESM.pdf (18 kb)
Supplementary Fig. 2. Mechanical response durations in control and oxaliplatin injected rats. Total response duration of spinal WDR neurons to cold acetone stimulation, but not to press or pinch stimulation, was augmented by oxaliplatin (A). High frequency response of neuronal firing was elicited by pinch (B) or press (C) within stimulation duration (3 s) in oxaliplatin-administered rats. No or little significant difference in firing rates after pinch (B) or press (C) stimulation was observed between control and oxaliplatin groups. N = 17 for control group and N = 21 for oxaliplatin group. *p < 0.05, **p < 0.01, ***p < 0.001, by unpaired t-test. (PDF 17 kb)


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Copyright information

© The Physiological Society of Japan and Springer Japan 2016

Authors and Affiliations

  1. 1.Department of PhysiologyCollege of Korean Medicine, Kyung Hee UniversitySeoulRepublic of Korea
  2. 2.Department of Information PhysiologyNational Institute for Physiological SciencesOkazakiJapan
  3. 3.School of Life ScienceThe Graduate University for Advanced Studies (SOKENDAI)OkazakiJapan

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