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Comparative Study
. 2013 Jan;18(1):130-6.
doi: 10.1007/s00776-012-0302-0. Epub 2012 Sep 21.

Different analgesic effects of adenosine between postoperative and neuropathic pain

Affiliations
Comparative Study

Different analgesic effects of adenosine between postoperative and neuropathic pain

Gotaro Yamaoka et al. J Orthop Sci. 2013 Jan.

Abstract

Background: Adenosine is an endogenous neuromodulator in both the peripheral and central nervous systems. Adenosine inhibits pain signals by hyperpolarizing neuronal membrane.

Methods: To clarify the effects of adenosine on pain signals, we tested intrathecal adenosine injection in two neuropathic pains (spinal cord compression and chronic constriction of sciatic nerve) and postoperative pain (plantar incision).

Results: In all three kinds of pain models, significant shortening of withdrawal latencies to thermal stimulation were detected from 24 h to 1 week after the surgery. Significant improvements of pain sensation were observed in all three models after intrathecal injection of Cl-adenosine 24 h after surgery. At 72 h after surgery, intrathecal Cl-adenosine injection inhibited hyperalgesia in the two neuropathic pain models but not in the postoperative pain model. Adenosine A1R messenger RNA (mRNA) expression significantly decreased in the plantar incision model. Adenosine A1R protein levels also decreased compared with the other two models and normal control.

Conclusions: These results suggest that adenosine effectively inhibits pain signals in neuropathic pain but is less effective in postoperative pain because of the decrease in adenosine A1 receptors.

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Figures

Fig. 1
Fig. 1
Time course of withdrawal latency by thermal stimulation following three kinds of pain models. After measurement of withdrawal latencies, rats received operations. Plantar incision (PI; n = 6), chronic constriction injury (CCI; n = 6), and spinal cord injury (SCI; n = 15) were performed. Measurements were taken every 24 h until the 7th day following operations. Data are the mean ± standard error of mean (SEM). Statistical significance compared with preoperation levels for each time point is represented with an asterisk (*P < 0.05)
Fig. 2
Fig. 2
Effects of Cl-adenosine on thermal stimulation in the plantar incision model at 24 h (a) and 72 h (b) after surgery. Data are mean ± standard error of mean (SEM) (n = 6 in each time point). Asterisk statistical significance (*P < 0.05)
Fig. 3
Fig. 3
Effects of Cl-adenosine on thermal stimulation in the chronic constriction injury model at 24 h (a) and 72 h (b) after surgery. Data are mean ± standard error of mean (SEM) (n = 6 in each time point). Asterisk statistical significance (*P < 0.05)
Fig. 4
Fig. 4
Effects of Cl-adenosine on thermal stimulation in the spinal cord injury model at 24 h (a) and 72 h (b) after surgery. Data are mean ± standard error of mean (SEM) (n = 6 in each time points). Asterisk, statistical significance compared vehicle animal (*P < 0.05)
Fig. 5
Fig. 5
Comparison of adenosine A1R messenger RNA (mRNA) expression by real-time polymerase chain reaction (PCR) analysis in the normal group and the three pain models. Data are mean ± standard error of mean (SEM) (n = 3 in each column). Asterisk statistical significance compared with normal group (*P < 0.05)
Fig. 6
Fig. 6
Adenosine A1R protein expression in spinal cord dorsal horn. Seventy-two hours after operation, spinal cord sections from the 11th vertebra of the spinal cord mild-compression (SCI) model and L4–L5 lumbar segment [lumbar enlargement; plantar incision (PI) and chronic constriction injury of sciatic nerve model (CCI) models and normal rat] were stained by anti-adenosine A1R antibody. Normal rat (a), PI model (b), CCI model (c), SCI model (d). Apparent decrease in adenosine A1R expression was observed in PI model

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