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Role of nitric oxide synthase in the development of bone cancer pain and effect of L‑NMMA

  • Authors:
    • Yan Yang
    • Juan Zhang
    • Yue Liu
    • Yaguo Zheng
    • Jinhua Bo
    • Xiaofang Zhou
    • Junhua Wang
    • Zhengliang Ma
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Affiliated Drum‑Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1220-1226
    |
    Published online on: December 7, 2015
       https://doi.org/10.3892/mmr.2015.4647
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Abstract

Spinal nitric oxide is involved in the mechanisms of pain generation and transmission during inflammatory and neuropathic pain. The aim of the present study was to explore the role of spinal nitric oxide in the development of bone cancer pain. 2x105 osteosarcoma cells were implanted into the intramedullary space of right femurs of C3H/HeJ mice to induce a model of ongoing bone cancer. Polymerase chain reaction and immunohistochemical analyses were performed to assess the expression of neuronal nitric oxide synthase (nNOS) and inducible (i)NOS in the spinal cord following inoculation. The results showed that inoculation of osteosarcoma cells induced progressive bone cancer, accompanied with pain‑associated behavior. The levels of nNOS mRNA in the spinal cord of tumor mice began to increase at day 10 and then decreased to the level in sham mice at day 14, while iNOS mRNA markedly increased in the tumor group at days 10 and 14. Immunohistochemical analysis showed that nNOS‑ and iNOS‑positive neurons were mainly located in the superficial dorsal horn and around the central canal of the L3‑L5 spinal cord. Intrathecal injection of 50 µg NOS inhibitor NG‑monomethyl‑l‑arginine (L‑NMMA) attenuated cancer‑evoked pain behaviors at day 14. These findings indicated that an upregulation of nNOS and iNOS in the spinal cord is associated with bone cancer pain and suggests that exogenously administered L‑NMMA may have beneficial effects to alleviate bone cancer pain.
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1 

Colvin L and Fallon M: Challenges in cancer pain management-bone pain. Eur J Cancer. 44:1083–1090. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Miyamoto T, Dubin AE, Petrus MJ and Patapoutian A: TRPV1 and TRPA1 mediate peripheral nitric oxide-induced nociception in mice. PLoS One. 4:e75962009. View Article : Google Scholar : PubMed/NCBI

3 

Naik AK, Tandan SK, Kumar D and Dudhgaonkar SP: Nitric oxide and its modulators in chronic constriction injury-induced neuropathic pain in rats. Eur J Pharmacol. 530:59–69. 2006. View Article : Google Scholar

4 

Guan Y, Yaster M, Raja SN and Tao YX: Genetic knockout and pharmacologic inhibition of neuronal nitric oxide synthase attenuate nerve injury-induced mechanical hypersensitivity in mice. Mol Pain. 3:292007. View Article : Google Scholar : PubMed/NCBI

5 

Tang Q, Svensson CI, Fitzsimmons B, Webb M, Yaksh TL and Hua XY: Inhibition of spinal constitutive NOS-2 by 1400W attenuates tissue injury and inflammation-induced hyperalgesia and spinal p38 activation. Eur J Neurosci. 25:2964–2972. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Choi JI, Kim WM, Lee HG, Kim YO and Yoon MH: Role of neuronal nitric oxide synthase in the antiallodynic effects of intrathecal EGCG in a neuropathic pain rat model. Neurosci Lett. 510:53–57. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Lam HH, Hanley DF, Trapp BD, Saito S, Raja S, Dawson TM and Yamaguchi H: Induction of spinal cord neuronal nitric oxide synthase (NOS) after formalin injection in the rat hind paw. Neurosci Lett. 210:201–204. 1996. View Article : Google Scholar : PubMed/NCBI

8 

Chacur M, Matos RJ, Alves AS, Rodrigues AC, Gutierrez V, Cury Y and Britto LR: Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection. Braz J Med Biol Res. 43:367–376. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Lee JS, Zhang Y and Ro JY: Involvement of neuronal, inducible and endothelial nitric oxide synthases in capsaicin-induced muscle hypersensitivity. Eur J Pain. 13:924–928. 2009. View Article : Google Scholar

10 

Handy RL and Moore PK: Effects of selective inhibitors of neuronal nitric oxide synthase on carrageenan-induced mechanical and thermal hyperalgesia. Neuropharmacology. 37:37–43. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Tanabe M, Nagatani Y, Saitoh K, Takasu K and Ono H: Pharmacological assessments of nitric oxide synthase isoforms and downstream diversity of NO signaling in the maintenance of thermal and mechanical hypersensitivity after peripheral nerve injury in mice. Neuropharmacology. 56:702–708. 2009. View Article : Google Scholar

12 

Chu YC, Guan Y, Skinner J, Raja SN, Johns RA and Tao YX: Effect of genetic knockout or pharmacologic inhibition of neuronal nitric oxide synthase on complete Freund's adjuvant-induced persistent pain. Pain. 119:113–123. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Toda N, Kishioka S, Hatano Y and Toda H: Modulation of opioid actions by nitric oxide signaling. Anesthesiology. 110:166–181. 2009. View Article : Google Scholar

14 

De Alba J, Clayton NM, Collins SD, Colthup P, Chessell I and Knowles RG: GW274150, a novel and highly selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), shows analgesic effects in rat models of inflammatory and neuropathic pain. Pain. 120:170–181. 2006. View Article : Google Scholar

15 

Sasaki A, Mabuchi T, Serizawa K, Takasaki I, Andoh T, Shiraki K, Ito S and Kuraishi Y: Different roles of nitric oxide synthase-1 and -2 between herpetic and postherpetic allodynia in mice. Neuroscience. 150:459–466. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Gu X, Zhang J, Ma Z, Wang J, Zhou X, Jin Y, Xia X, Gao Q and Mei F: The role of N-methyl-D-aspartate receptor subunit NR2B in spinal cord in cancer pain. Eur J Pain. 14:496–502. 2010. View Article : Google Scholar

17 

Meller ST and Gebhart GF: Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain. 52:127–136. 1993. View Article : Google Scholar : PubMed/NCBI

18 

Ma ZL, Zhang W, Gu XP, Yang WS and Zeng YM: Effects of intrathecal injection of prednisolone acetate on expression of NR2B subunit and nNOS in spinal cord of rats after chronic compression of dorsal root ganglia. Ann Clin Lab Sci. 37:349–355. 2007.PubMed/NCBI

19 

Zimmermann M: Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 16:109–110. 1983. View Article : Google Scholar : PubMed/NCBI

20 

Schwei MJ, Honore P, Rogers SD, Salak-Johnson JL, Finke MP, Ramnaraine ML, Clohisy DR and Mantyh PW: Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. J Neurosci. 19:10886–10897. 1999.PubMed/NCBI

21 

Hylden JL and Wilcox GL: Intrathecal morphine in mice: A new technique. Eur J Pharmacol. 67:313–316. 1980. View Article : Google Scholar : PubMed/NCBI

22 

Chaplan SR, Bach FW, Pogrel JW, Chung JM and Yaksh TL: Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 53:55–63. 1994. View Article : Google Scholar : PubMed/NCBI

23 

Hargreaves K, Dubner R, Brown F, Flores C and Joris J: A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 32:77–88. 1988. View Article : Google Scholar : PubMed/NCBI

24 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar

25 

Dolan S, Kelly JG, Huan M and Nolan AM: Transient up-regulation of spinal cyclooxygenase-2 and neuronal nitric oxide synthase following surgical inflammation. Anesthesiology. 98:170–180. 2003. View Article : Google Scholar

26 

Conti A, Miscusi M, Cardali S, Germanò A, Suzuki H, Cuzzocrea S and Tomasello F: Nitric oxide in the injured spinal cord: Synthases cross-talk, oxidative stress and inflammation. Brain Res Rev. 54:205–218. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Martucci C, Trovato AE, Costa B, Borsani E, Franchi S, Magnaghi V, Panerai AE, Rodella LF, Valsecchi AE, Sacerdote P and Colleoni M: The purinergic antagonist PPADS reduces pain related behaviours and interleukin-1 beta, interleukin-6, iNOS and nNOS overproduction in central and peripheral nervous system after peripheral neuropathy in mice. Pain. 137:81–95. 2008. View Article : Google Scholar

28 

Pedersen LM, Jacobsen LM, Mollerup S and Gjerstad J: Spinal cord long-term potentiation (LTP) is associated with increased dorsal horn gene expression of IL-1beta, GDNF and iNOS. Eur J Pain. 14:255–260. 2010. View Article : Google Scholar

29 

Guhring H, Tegeder I, Lötsch J, Pahl A, Werner U, Reeh PW, Rehse K, Brune K and Geisslinger G: Role of nitric oxide in zymosan induced paw inflammation and thermal hyperalgesia. Inflamm Res. 50:83–88. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Aley KO, McCarter G and Levine JD: Nitric oxide signaling in pain and nociceptor sensitization in the rat. J Neurosci. 18:7008–7014. 1998.PubMed/NCBI

31 

Malmberg AB and Yaksh TL: Spinal nitric oxide synthesis inhibition blocks NMDA-induced thermal hyperalgesia and produces antinociception in the formalin test in rats. Pain. 54:291–300. 1993. View Article : Google Scholar : PubMed/NCBI

32 

Yonehara N, Kudo C and Kamisaki Y: Involvement of NMDA-nitric oxide pathways in the development of tactile hypersensitivity evoked by the loose-ligation of inferior alveolar nerves in rats. Brain Res. 963:232–243. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Ashina M, Lassen LH, Bendtsen L, Jensen R and Olesen J: Effect of inhibition of nitric oxide synthase on chronic tension-type headache: A randomised crossover trial. Lancet. 353:287–289. 1999. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang Y, Zhang J, Liu Y, Zheng Y, Bo J, Zhou X, Wang J and Ma Z: Role of nitric oxide synthase in the development of bone cancer pain and effect of L‑NMMA. Mol Med Rep 13: 1220-1226, 2016.
APA
Yang, Y., Zhang, J., Liu, Y., Zheng, Y., Bo, J., Zhou, X. ... Ma, Z. (2016). Role of nitric oxide synthase in the development of bone cancer pain and effect of L‑NMMA. Molecular Medicine Reports, 13, 1220-1226. https://doi.org/10.3892/mmr.2015.4647
MLA
Yang, Y., Zhang, J., Liu, Y., Zheng, Y., Bo, J., Zhou, X., Wang, J., Ma, Z."Role of nitric oxide synthase in the development of bone cancer pain and effect of L‑NMMA". Molecular Medicine Reports 13.2 (2016): 1220-1226.
Chicago
Yang, Y., Zhang, J., Liu, Y., Zheng, Y., Bo, J., Zhou, X., Wang, J., Ma, Z."Role of nitric oxide synthase in the development of bone cancer pain and effect of L‑NMMA". Molecular Medicine Reports 13, no. 2 (2016): 1220-1226. https://doi.org/10.3892/mmr.2015.4647
Copy and paste a formatted citation
x
Spandidos Publications style
Yang Y, Zhang J, Liu Y, Zheng Y, Bo J, Zhou X, Wang J and Ma Z: Role of nitric oxide synthase in the development of bone cancer pain and effect of L‑NMMA. Mol Med Rep 13: 1220-1226, 2016.
APA
Yang, Y., Zhang, J., Liu, Y., Zheng, Y., Bo, J., Zhou, X. ... Ma, Z. (2016). Role of nitric oxide synthase in the development of bone cancer pain and effect of L‑NMMA. Molecular Medicine Reports, 13, 1220-1226. https://doi.org/10.3892/mmr.2015.4647
MLA
Yang, Y., Zhang, J., Liu, Y., Zheng, Y., Bo, J., Zhou, X., Wang, J., Ma, Z."Role of nitric oxide synthase in the development of bone cancer pain and effect of L‑NMMA". Molecular Medicine Reports 13.2 (2016): 1220-1226.
Chicago
Yang, Y., Zhang, J., Liu, Y., Zheng, Y., Bo, J., Zhou, X., Wang, J., Ma, Z."Role of nitric oxide synthase in the development of bone cancer pain and effect of L‑NMMA". Molecular Medicine Reports 13, no. 2 (2016): 1220-1226. https://doi.org/10.3892/mmr.2015.4647
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