Skip to main content

Advertisement

Log in

Changes in Purines Concentration in the Cerebrospinal Fluid of Pregnant Women Experiencing Pain During Active Labor

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Labor pain has been reported as a severe pain and can be considered as a model of acute visceral pain. It is well known that extracellular purines have an important role in pain signaling in the central nervous system. This study analyzes the relationship between extracellular purines and pain perception during active labor. A prospective observational study was performed. Cerebrospinal fluid (CSF) levels of the purines and their metabolites were compared between women at term pregnancy with labor pain (n = 49) and without labor pain (Caesarian section; n = 47). Control groups (healthy men and women without chronic or acute pain—n = 40 and 32, respectively) were also investigated. The CSF levels of adenosine were significantly lower in the labor pain group (P = 0.026) and negatively correlated with pain intensity measured by a visual analogue scale (r = −0.48, P = 0.0005). Interestingly, CSF levels of uric acid were significantly higher in healthy men as compared to women. Additionally, pregnant women showed increased CSF levels of ADP, GDP, adenosine and guanosine and reduced CSF levels of AMP, GTP, and uric acid as compared to non-pregnant women (P < 0.05). These findings suggest that purines, in special the nucleoside adenosine, are associated with pregnancy and labor pain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Melzack R (1993) Labor pain as a model of acute pain. Pain 53:117–120

    Article  CAS  PubMed  Google Scholar 

  2. Sawynok J (1998) Adenosine receptor activation and nociception. Eur J Clin Pharmacol 317:1–11

    Article  Google Scholar 

  3. Sawynok J, Liu XJ (2003) Adenosine in the spinal cord and periphery: release and regulation of pain. Prog Neurobiol 69:313–340

    Article  CAS  PubMed  Google Scholar 

  4. Inoue K, Tsuda M, Koizumi S (2005) ATP receptors in pain sensation: involvement of spinal microglia and P2X(4) receptors. Purinergic Signal 1:95–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797

    Article  CAS  PubMed  Google Scholar 

  6. Sawynok J, Reid A, Liu XJ (1999) Acute paw oedema induced by local injection of adenosine A(1), A(2) and A(3) receptor agonists. Eur J Pharmacol 386:253–261

    Article  CAS  PubMed  Google Scholar 

  7. Dickenson AH, Suzuki R, Reeve AJ (2000) Adenosine as a potential analgesic target in inflammatory and neuropathic pains. CNS Drugs 13:77–85

    Article  CAS  Google Scholar 

  8. Castro-Gago M, Cid E, Trabazo S, Pavón P, Camiña F, Rodríguez-Segade S, Einís Puñal J, Rodríguez-Nuñez A (1995) Cerebrospinal fluid purine metabolites and pyrimidine bases after brief febrile convulsions. Epilepsia 36:471–474

    Article  CAS  PubMed  Google Scholar 

  9. Rodríguez-Núñez A, Cid E, Rodríguez-García J, Camiña F, Rodríguez-Segade S, Castro-Gago M (2000) Cerebrospinal fluid purine metabolite and neuron-specific enolase concentrations after febrile seizures. Brain Dev 22:427–431

    Article  PubMed  Google Scholar 

  10. Palmer AM, Marion DW, Botscheller ML, Bowen DM, DeKosky ST (1994) Increased transmitter amino acid concentration in human ventricular CSF after brain trauma. NeuroReport 6:153–156

    Article  CAS  PubMed  Google Scholar 

  11. Sethuraman R, Lee TL, Chui JW, Tachibana S (2006) Changes in amino acids and nitric oxide concentration in cerebrospinal fluid during labor pain. Neurochem Res 31:1127–1133

    Article  CAS  PubMed  Google Scholar 

  12. Olofsson C, Ekblom A, Ekman-Ordeberg G, Irestedt L, Nyberg F, Ungerstedt U, Wiklund P (1997) Increased cerebrospinal fluid concentration of aspartate but decreased concentration of nitric oxide breakdown products in women experiencing visceral pain during active labour. NeuroReport 8:995–998

    Article  CAS  PubMed  Google Scholar 

  13. Hsu MM, Chou YY, Chang YC, Chou TC, Wong CS (2001) An analysis of excitatory amino acids, nitric oxide, and prostaglandin E2 in the cerebrospinal fluid of pregnant women: the effect on labor pain. Anesth Analg 93:1293–1296

    Article  CAS  PubMed  Google Scholar 

  14. Larson AA, Giovengo SL, Russell IJ, Michalek JE (2000) Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways. Pain 87:201–211

    Article  CAS  PubMed  Google Scholar 

  15. Alexander GM, Perreault MJ, Reichenberger ER, Schwartzman RJ (2007) Changes in immune and glial markers in the CSF of patients with complex regional pain syndrome. Brain Behav Immun 21:668–676

    Article  CAS  PubMed  Google Scholar 

  16. Sarchielli P, Mancini ML, Floridi A, Coppola F, Rossi C, Nardi K, Acciarresi M, Pini LA, Calabresi P (2007) Increased levels of neurotrophins are not specific for chronic migraine: evidence from primary fibromyalgia syndrome. J Pain 8:737–745

    Article  CAS  PubMed  Google Scholar 

  17. Regner A, Crestana RE, Silveira FJP, Friedman G, Chemale I, Souza D (1997) Guanine nucleotides are present in human CSF. NeuroReport 8:3771–3774

    Article  CAS  PubMed  Google Scholar 

  18. Schmidt AP, Böhmer AE, Soares FA, Posso IP, Machado SB, Mendes FF, Portela LV, Souza DO (2010) Changes in purines concentration in the cerebrospinal fluid of patients experiencing pain: a case-control study. Neurosci Lett 474:69–73

    Article  CAS  PubMed  Google Scholar 

  19. Schmidt AP, Valinetti EA, Bandeira D, Bertacchi MF, Simões CM, Auler JO Jr (2007) Effects of preanesthetic administration of midazolam, clonidine, or dexmedetomidine on postoperative pain and anxiety in children. Paediatr Anaesth 17:667–674

    Article  PubMed  Google Scholar 

  20. Scott J, Huskisson EC (1976) Graphic representation of pain. Pain 2:175–184

    Article  CAS  PubMed  Google Scholar 

  21. Collins SL, Moore RA, McQuay HJ (1997) The visual analogue pain intensity scale: what is moderate pain in millimetres? Pain 72:95–97

    Article  CAS  PubMed  Google Scholar 

  22. Domanski L, Sulikowski T, Safranow K, Pawlik A, Olszewska M, Chlubek D, Urasinska E, Ciechanowski K (2006) Effect of trimetazidine on the nucleotide profile in rat kidney with ischemia-reperfusion injury. Eur J Pharm Sci 27:320–327

    Article  CAS  PubMed  Google Scholar 

  23. Kawabe M, Sato A, Hoshi T, Sakai S, Hiraya D, Watabe H, Kakefuda Y, Ishibashi M, Abe D, Takeyasu N, Aonuma K (2015) Gender differences in the association between serum uric acid and prognosis in patients with acute coronary syndrome. J Cardiol. doi:10.1016/j.jjcc.2015.05.009

    Google Scholar 

  24. Zimmermann H (2001) Ectonucleotidases: some recent developments and note on nomenclature. Drug Dev Res 52:46–56

    Article  Google Scholar 

  25. Cruz Portela LV, Oses JP, Silveira AL, Schmidt AP, Lara DR, Oliveira Battastini AM, Ramirez G, Vinadé L, Freitas Sarkis JJ, Souza DO (2002) Guanine and adenine nucleotidase activities in rat cerebrospinal fluid. Brain Res 950:74–78

    Article  PubMed  Google Scholar 

  26. Oses JP, Leke R, Portela LV, Lara DR, Schmidt AP, Casali EA, Wofchuk S, Souza DO, Sarkis JJ (2004) Biochemical brain markers and purinergic parameters in rat CSF after seizure induced by pentylenetetrazol. Brain Res Bull 64:237–242

    Article  CAS  PubMed  Google Scholar 

  27. Mihaylova-Todorova ST, Todorov LD, Westfall DP (2002) Enzyme kinetics and pharmacological characterization of nucleotidases released from the guinea pig isolated vas deferens during nerve stimulation: evidence for a soluble ecto-nucleoside triphosphate diphosphohydrolase-like ATPase and a soluble ecto-5′-nucleotidase like-AMPase. J Pharmacol Exp Ther 302:992–1001

    Article  CAS  PubMed  Google Scholar 

  28. Nakano H, Furuya K, Yamagishi S (2001) Synergistic effects of ATP on oxytocin-induced intracellular Ca2+ response in mouse mammary myoepithelial cells. Pflugers Arch 442:57–63

    Article  CAS  PubMed  Google Scholar 

  29. Blaug S, Rymer J, Jalickee S, Miller SS (2003) P2 purinoceptors regulate calcium-activated chloride and fluid transport in 31EG4 mammary epithelia. Am J Physiol Cell Physiol 284:C897–C909

    Article  CAS  PubMed  Google Scholar 

  30. Gorodeski GI (2002) Regulation of transcervical permeability by two distinct P2 purinergic receptor mechanisms. Am J Physiol Cell Physiol 282:C75–C83

    CAS  PubMed  Google Scholar 

  31. Liu XJ, Salter MW (2005) Purines and pain mechanisms: recent developments. Curr Opin Investig Drugs 6:65–75

    PubMed  Google Scholar 

  32. Boison D (2008) Adenosine as a neuromodulator in neurological diseases. Curr Opin Pharmacol 8:2–7

    Article  CAS  PubMed  Google Scholar 

  33. Gebicke-Haerter PJ, Christoffel F, Timmer J, Northoff H, Berger M, Van Calker D (1996) Both adenosine A1- and A2-receptors are required to stimulate microglial proliferation. Neurochem Int 29:37–42

    Article  CAS  PubMed  Google Scholar 

  34. Liao SL, Chen CJ (2001) Differential effects of cytokines and redox potential on glutamate uptake in rat cortical glial cultures. Neurosci Lett 299:113–116

    Article  CAS  PubMed  Google Scholar 

  35. Watkins LR, Maier SF (2003) Glia: a novel drug discovery target for clinical pain. Nat Rev Drug Discov 2:973–985

    Article  CAS  PubMed  Google Scholar 

  36. Watkins LR, Milligan ED, Maier SF (2001) Glial activation: a driving force for pathological pain. Trends Neurosci 24:450–455

    Article  CAS  PubMed  Google Scholar 

  37. Millan MJ (1999) The induction of pain: an integrative review. Prog Neurobiol 57:1–164

    Article  CAS  PubMed  Google Scholar 

  38. Lasley RD (2011) Adenosine receptors and membrane microdomains. Biochim Biophys Acta 1808:1284–1289

    Article  CAS  PubMed  Google Scholar 

  39. Schmidt AP, Lara DR, Souza DO (2007) Proposal of a guanine-based purinergic system in the mammalian central nervous system. Pharmacol Ther 116:401–416

    Article  CAS  PubMed  Google Scholar 

  40. Schmidt AP, Böhmer AE, Leke R, Schallenberger C, Antunes C, Pereira MS, Wofchuk ST, Elisabetsky E, Souza DO (2008) Antinociceptive effects of intracerebroventricular administration of guanine-based purines in mice: evidences for the mechanism of action. Brain Res 1234:50–58

    Article  CAS  PubMed  Google Scholar 

  41. Schmidt AP, Böhmer AE, Schallenberger C, Antunes C, Tavares RG, Wofchuk ST, Elisabetsky E, Souza DO (2010) Mechanisms involved in the antinociception induced by systemic administration of guanosine in mice. Br J Pharmacol 159:1247–1263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Schmidt AP, Paniz L, Schallenberger C, Böhmer AE, Wofchuk ST, Elisabetsky E, Portela LV, Souza DO (2010) Guanosine prevents thermal hyperalgesia in a rat model of peripheral mononeuropathy. J Pain 11:131–141

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by the Brazilian research agencies FINEP, CNPq, CAPES, FAPERGS, UFRGS and INCT for Excitotoxicity and Neuroprotection (INCTEN/CNPq).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to André P. Schmidt.

Ethics declarations

Conflict of interest

The authors have no competing interests.

Additional information

Implications Statement This study demonstrated that the CSF levels of adenosine were significantly reduced in pregnant women experiencing pain during active labor. These findings suggest that purines, in special the nucleoside adenosine, are associated with pregnancy and labor pain.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schmidt, A.P., Böhmer, A.E., Hansel, G. et al. Changes in Purines Concentration in the Cerebrospinal Fluid of Pregnant Women Experiencing Pain During Active Labor. Neurochem Res 40, 2262–2269 (2015). https://doi.org/10.1007/s11064-015-1716-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-015-1716-9

Keywords

Navigation