Painful Nerve Injury Shortens the Intracellular Ca2+ Signal in Axotomized Sensory Neurons of Rats

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Abstract

Background:

Neuropathic pain is inadequately treated and poorly understood at the cellular level. Because intracellular Ca2+ signaling critically regulates diverse neuronal functions, the authors examined effects of peripheral nerve injury on the Ca2+ transient that follows neuronal activation.

Methods:

Cytoplasmic Ca2+ levels were recorded by digital microfluorometry from dissociated dorsal root ganglion neurons of hyperalgesic animals after ligation of the fifth lumbar spinal nerve and control animals. Neurons were activated by field stimulation or by K+ depolarization.

Results:

Transients in presumptively nociceptive, small, capsaicin-sensitive neurons were diminished after axotomy, whereas transient amplitude increased in axotomized nonnociceptive neurons. Axotomy diminished the upward shift in resting calcium after transient recovery. In contrast, nociceptive neurons adjacent to axotomy acquired increased duration of the transient and greater baseline shift after K+ activation. Transients of nonnociceptive neurons adjacent to axotomy showed no changes after injury. In nociceptive neurons from injured rats that did not develop hyperalgesia, transient amplitude and baseline offset were large after axotomy, whereas transient duration in the adjacent neurons was shorter compared with neurons excised from hyperalgesic animals, which show normalization of these features.

Conclusions:

A diminished Ca2+ signal in axotomized neurons may be in part due to loss of Ca2+ influx through voltage-gated Ca2+ channels. The upward shift in resting Ca2+ level after activation, which is diminished after axotomy in presumed nociceptive neurons, is a previously unrecognized aspect of neuronal plasticity. These changes in the critical Ca2+ signal may mediate various injury-related abnormalities in Ca2+-dependent neuronal.

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