Establishment of postoperative sustained injury sensitization model of inflammatory pain-sensitivity

doi:10.3877/cma.j.issn.1674-0793.2018.01.003

Abstract

Abstract:

Objective

To investigate the effects of spinal PKMζ on the maintenance of persistent nociceptive sensitization after plantar incision following peripheral inflammation in rats, adapting a modified hyperalgesia priming model that produces a state of sensitization closely resembling clinical situations with increased risk of development of persistent postoperative pain.

Methods

Twenty-eight healthy adult male Sprague-Dawley rats weighing 220-250 gram were randomly divided into two groups (n=14): NS+Surgery group which was induced by intraplantar injection of carrageenan (1%, 5 μl), and Car.+Surgery group with NS (0.9%NaCl, 5 μl) into one hindpaw in rats. Changes of pain behavior were assessed by withdrawal threshold to von Frey filament stimulation intensity, response latency of the hindpaw to radiant the thermal and a cumulative pain scores 1-6 d before incision as well as 1-10 d after incision. The expression of PKMζ was measured in the spinal cord by Western blotting and immunohistochemical analysis at 1, 3, 10 d after incision.

Results

There were no significant differences in the value of MWT and TWL before treatment and surgery. Compared with NS+ Surgery group, the MWT and TWL of Car.+Surgery group decreased significantly (P<0.05), which lasted about 3 d and returned to normal. All rats showed allodynia in response to innocuous mechanical stimulation. Compared with pre-incision, the MWT and TWL of two groups decreased significantly (P<0.05). While the MWT and TWL of NS+Surgery group increased thereafter and returned to normal by 6 d. Compared with pre-incision and NS+Surgery group, the MWT and TWL of Car.+Surgery group decreased significantly, lasting for 10 d (P<0.05). Compared with NS+Surgery group, the number of positive cells and the expression of spinal PKMζ after incision remarkably increased in Car.+Surgery group (P<0.05).

Conclusion

Spinal PKMζ involves in the development and maintenance of persistent nociceptive sensitization after plantar incision following peripheral inflammation pain in rats.

Key words: Protein kinases, Spinal cord, Models, animal, Persistent nociceptive sensitization

Kunhe Li, Yi Li, Lijun Niu, Guang Yang, Qing Zhao, Zhishuang Wen, Jinjun Zhang, Ke An. Establishment of postoperative sustained injury sensitization model of inflammatory pain-sensitivity[J]. Chinese Archives of General Surgery(Electronic Edition), 2018, 12(01): 9-13.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhptwkxwx.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0793.2018.01.003

https://zhptwkxwx.cma-cmc.com.cn/EN/Y2018/V12/I01/9

Figures/Tables 10

References 19

[1]	Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention[J]. Lancet, 2006, 367(9522): 1618-1625.
[2]	Niraj G, Rowbotham DJ. Persistent postsurgical pain: where are we now?[J]. Br J Anaesth, 2011, 107(1): 25-29.
[3]	Johansen A, Romundstad L, Nielsen CS, et al. Persistent postsurgical pain in a general population: prevalence and predictors in the Tromso study[J]. Pain, 2012, 153(7): 1390-1396.
[4]	Aasvang EK, Gmaehle E, Hansen JB, et al. Predictive risk factors for persistent postherniotomy pain[J]. Anesthesiology, 2010, 112(4): 957-969.
[5]	Hamalainen MM, Gebhart GF, Brennan TJ. Acute effect of an incision on mechanosensitive afferents in the plantar rat hindpaw[J]. J Neurophysiol, 2002, 87(2): 712-720.
[6]	Pogatzki EM, Gebhart GF, Brennan TJ. Characterization of Adelta- and C-fibers innervating the plantar rat hindpaw one day after an incision[J]. J Neurophysiol, 2002, 87(2): 721-731.
[7]	Vandermeulen EP, Brennan TJ. Alterations in ascending dorsal horn neurons by a surgical incision in the rat foot[J]. Anesthesiology, 2000, 93(5): 1294-1302, 6A.
[8]	Melosh HJ, Schneider NM, Zahnle KJ, et al. Ignition of global wildfires at the Cretaceous/Tertiary boundary[J]. Nature, 1990, 343(6255): 251-254.
[9]	Aley KO, Messing RO, Mochly-Rosen D, et al. Chronic hypersensitivity for inflammatory nociceptor sensitization mediated by the epsilon isozyme of protein kinase C[J]. J Neurosci, 2000, 20(12): 4680-4685.
[10]	Brennan TJ, Vandermeulen EP, Gebhart GF. Characterization of a rat model of incisional pain[J]. Pain, 1996, 64(3): 493-501.
[11]	Ling DS, Benardo LS, Sacktor TC. Protein kinase Mzeta enhances excitatory synaptic transmission by increasing the number of active postsynaptic AMPA receptors[J]. Hippocampus, 2006, 16(5): 443-452.
[12]	Asiedu MN, Tillu DV, Melemedjian OK, et al. Spinal protein kinase Mζ underlies the maintenance mechanism of persistent nociceptive sensitization[J]. J Neurosci, 2011, 31(18): 6646-6653.
[13]	Chaplan SR, Bach FW, Pogrel JW, et al. Quantitative assessment of tactile allodynia in the rat paw[J]. J Neurosci Methods, 1994, 53(1): 55-63.
[14]	Perkins FM, Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors[J]. Anesthesiology, 2000, 93(4): 1123-1133.
[15]	Stamford JA. Descending control of pain[J]. Br J Anesth, 1995, 75(2): 217-227．
[16]	Kuner R. Central mechanisms of pathological pain[J]. Nat Med, 2010, 16(11): 1258-1266.
[17]	Sandkuhler J, Liu X. Induction of long-term potentiation at spinal synapses by noxious stimulation or nerve injury[J]. Eur J Neurosci, 1998, 10(7): 2476-2480．
[18]	Ikeda H, Stark J, Fischer H, et al. Synaptic amplifier of inflammatory pain in the spinal dorsal horn[J]. Science, 2006, 312(5780): 1659-1662.
[19]	Ikeda H, Heinke B, Ruscheweyh R, et al. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia[J]. Science, 2003, 299(5610): 1237-1240.

时间点（d）	非触发组	触发组	t值	P值
1	14.4±2.2	14.4±3.4	0.000	1.000
2	14.1±4.1	7.3±4.5	4.179	0.000
3	14.9±3.7	9.8±3.4	3.798	0.001
4	14.3±6.4	13.9±4.9	0.186	0.854
5	14.5±7.1	14.5±5.6	0.000	1.000
6	14.7±1.1	14.4±4.5	0.242	0.810
7	4.4±4.1	4.3±4.5	0.062	0.951
8	6.9±4.9	3.8±3.4	1.945	0.063
9	12.8±6.4	3.7±4.9	4.224	0.000
11	13.8±7.1	3.8±5.2	4.252	0.000
13	14.0±4.9	4.1±4.9	5.345	0.000
16	14.5±4.5	4.8±5.6	5.052	0.000

时间点（d）	非触发组	触发组	t值	P值
1	14.4±2.2	14.4±3.4	0.000	1.000
2	14.1±4.1	7.3±4.5	4.179	0.000
3	14.9±3.7	9.8±3.4	3.798	0.001
4	14.3±6.4	13.9±4.9	0.186	0.854
5	14.5±7.1	14.5±5.6	0.000	1.000
6	14.7±1.1	14.4±4.5	0.242	0.810
7	4.4±4.1	4.3±4.5	0.062	0.951
8	6.9±4.9	3.8±3.4	1.945	0.063
9	12.8±6.4	3.7±4.9	4.224	0.000
11	13.8±7.1	3.8±5.2	4.252	0.000
13	14.0±4.9	4.1±4.9	5.345	0.000
16	14.5±4.5	4.8±5.6	5.052	0.000

时间点（d）	非触发组	触发组	t值	P值
1	15.5±4.5	15.5±1.9	0.000	1.000
2	15.5±4.5	8.8±3.7	4.303	0.000
3	14.8±3.7	10.9±3.4	2.904	0.007
4	15.1±5.2	15.0±6.0	0.047	0.963
5	14.8±4.9	15.1±5.6	-0.151	0.881
6	15.4±4.9	15.5±3.4	-0.063	0.950
7	8.2±6.4	7.8±5.6	0.176	0.862
8	12.6±5.2	5.5±6.4	3.222	0.003
9	14.2±5.6	6.1±7.1	3.352	0.002
11	14.9±3.7	6.2±6.4	4.403	0.000
13	14.6±6.7	6.9±6.0	3.203	0.004
16	14.8±6.4	7.2±6.0	3.241	0.003

时间点（d）	非触发组	触发组	t值	P值
1	15.5±4.5	15.5±1.9	0.000	1.000
2	15.5±4.5	8.8±3.7	4.303	0.000
3	14.8±3.7	10.9±3.4	2.904	0.007
4	15.1±5.2	15.0±6.0	0.047	0.963
5	14.8±4.9	15.1±5.6	-0.151	0.881
6	15.4±4.9	15.5±3.4	-0.063	0.950
7	8.2±6.4	7.8±5.6	0.176	0.862
8	12.6±5.2	5.5±6.4	3.222	0.003
9	14.2±5.6	6.1±7.1	3.352	0.002
11	14.9±3.7	6.2±6.4	4.403	0.000
13	14.6±6.7	6.9±6.0	3.203	0.004
16	14.8±6.4	7.2±6.0	3.241	0.003

组别	0 d	1 d	3 d	10 d
非触发组	0.92±0.24	0.80±0.25	0.91±0.23	0.92±0.34
触发组	0.93±0.12	1.24±0.11	1.32±0.32	1.38±0.34
t值	-0.139	-6.236	-3.893	-3.579
P值	0.890	0.000	0.001	0.001

Please choose a citation manager

Content to export