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Updated: Jul 31, 2026
Operant Sensation Seeking in the Mouse
Published on: November 10, 2010
Downregulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain
Makoto Tsuda1, Yukari Shigemoto-Mogami, Shinya Ueno
1Section of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Abstract:
There is large variability in the various pain responses including those to tissue injury among inbred mouse strains. However, the determinant factors for the strain-specific differences remain unknown. The P2X3 sensory-specific ATP-gated channel has been implicated as a damage-sensing molecule that evokes a pain sensation by receiving endogenous ATP from injured tissue. In this study, to clarify the contribution of the sensory P2X3 signalling to strain-specific differences in tissue injury pain, we examined whether the P2X3-mediated in vivo and in vitro responses in dorsal root ganglion (DRG) neurons are changed in the A/J inbred mouse strain, which is known to be resistant to tissue injury pain caused by formalin. Here we found that A/J mice exhibited a low magnitude of nocifensive behaviour induced by the P2X agonist alpha,beta-methylene ATP (alpha beta meATP) into the hindpaw compared with C57BL/6 J mice. This behaviour was blocked by P2X3 antisense oligodeoxynucleotides. The low magnitude of the in vivo pain sensation could be observed similarly in the in vitro response; the increase in the intracellular Ca(2+) increase by alpha beta meATP in capsaicin-sensitive DRG neurons from A/J mice was significantly lower than that from C57BL/6 J mice. In A/J DRG neurons the P2X3 protein level was significantly lower compared with C57BL/6 J DRG neurons. The change in P2X3 protein was selective because P2X2 protein was expressed equally in both strains. The present study suggests that the downregulation of sensory P2X3 could be one of the molecular predispositions to low sensitivity to tissue injury pain in the A/J inbred mouse strain.
Insights
A/J mice show reduced pain sensitivity due to lower P2X3 protein levels. This downregulation of the P2X3 channel in sensory neurons contributes to their resistance to tissue injury pain.
Area of Science:
- Neuroscience
- Pain Research
- Genetics
Background:
- Inbred mouse strains exhibit significant variability in pain responses to tissue injury.
- The underlying genetic factors contributing to these strain-specific pain differences are largely unknown.
- The P2X3 channel is a key sensor of tissue damage, detecting endogenous ATP and mediating pain signals.
Purpose of the Study:
- To investigate the role of P2X3 signaling in strain-specific differences in tissue injury pain.
- To determine if P2X3-mediated responses are altered in the A/J mouse strain, known for its pain resistance.
Main Methods:
- Compared nocifensive behavior induced by P2X agonist alpha,beta-methylene ATP (alpha beta meATP) in A/J and C57BL/6 J mice.
- Administered P2X3 antisense oligodeoxynucleotides to assess the role of P2X3 in pain behavior.
- Measured intracellular Ca(2+) in dorsal root ganglion (DRG) neurons in response to alpha beta meATP in vitro.
- Quantified P2X3 and P2X2 protein levels in DRG neurons from both strains.
Main Results:
- A/J mice displayed significantly lower nocifensive behavior in response to alpha beta meATP compared to C57BL/6 J mice.
- This reduced pain behavior was blocked by P2X3 antisense oligodeoxynucleotides.
- In vitro, A/J DRG neurons showed a significantly lower intracellular Ca(2+) increase upon alpha beta meATP stimulation.
- A/J mice had significantly lower P2X3 protein levels in DRG neurons, while P2X2 levels were comparable to C57BL/6 J mice.
Conclusions:
- Downregulation of sensory P2X3 protein is a potential molecular basis for the reduced sensitivity to tissue injury pain observed in A/J mice.
- These findings highlight the critical role of P2X3 signaling in mediating pain perception and contributing to strain-specific pain phenotypes.
