Elsevier

Neuroscience

Volume 110, Issue 3, 20 March 2002, Pages 569-578
Neuroscience

The expression of Fos-labeled spinal neurons in response to colorectal distension is enhanced after chronic spinal cord transection in the rat

https://doi.org/10.1016/S0306-4522(01)00548-6Get rights and content

Abstract

The present study used Fos-like immunoreactivity to examine neuronal activation in response to colorectal distension in rats at 1 day or 30 days following spinal cord transection or sham transection. Fifty-five Wistar rats were anesthetized and an incision was made to expose the T5 spinal segment. The dura was reflected away in all rats and a complete transection at the rostral end of the T5 segment was given to the lesioned group. At 1 day (acute) or 30 days (chronic) post-surgery, conscious rats were subjected to a 2 h period of intermittent colorectal distension. Rats were perfused and spinal segments L5–S2 were removed and processed for Fos-like immunoreactivity. Spinal cord transection alone had no effect on Fos-labeling in either acute or chronic rats. In acute rats, colorectal distension produced significant increases in Fos-labeling in the superficial and deep dorsal horn regions. In chronic rats, colorectal distension produced a three-fold increase in Fos-labeled neurons that was manifest throughout all laminar regions.

These results indicate that the number of neurons expressing Fos in response to colorectal distension is much greater after a chronic spinal cord transection than after an acute transection. Since Fos is an indicator of neuronal activation, the results show that many more neurons become active in response to colorectal distension following a chronic spinal injury. This suggests that a functional reorganization of spinal circuits occurs following chronic spinal cord transection. This may ultimately result in altered visceral and somatic functions associated with spinal cord injury in humans.

Section snippets

Experimental procedures

Experiments were performed at 1 day or 30 days post-surgery in 55 male Wistar rats (Charles River; Wilmington, MA, USA) ranging in weight from 340 to 500 g. All procedures were approved by the University of Oklahoma Health Sciences Center Institutional Animal Care and Use Committee, and conformed with the National Institutes of Health guide for the care and use of laboratory animals. All efforts were made to minimize animal suffering and to minimize the number of animals necessary to produce

Total numbers of Fos-labeled neurons for 1 day and 30 day groups

Neurons demonstrating Fos-like immunoreactivity were analyzed for spinal segments L5–S2. Fos-labeled neurons were most densely located between the segments of L6 and the rostral end of S1 with the fewest number of labeled neurons in the S2 segment. Sample sections of tissue which show the locations of labeled neurons in 1 day and 30 day rats are illustrated in Fig. 2, Fig. 3, respectively. The five regions of the spinal cord that were analyzed are also designated in these figures. Group means

Discussion

The purpose of this study was to examine changes in neuronal activation in response to CRD in an acute and chronic model of spinal cord injury. Of particular interest were potential changes in chronic lesioned animals as an indicator of plasticity that ultimately results in the myriad functional changes that occur following spinal cord injury. Our results indicate that approximately three times as many neurons respond to CRD after chronic spinal cord injury compared to neurally intact animals.

Conclusions

In summary, we found a profound increase in the number of neurons expressing Fos in response to CRD following a chronic spinal cord injury. This response may represent a functional anatomical reorganization of spinal cord circuitry that ultimately underlies the functional alterations associated with chronic spinal cord injury in humans.

Acknowledgements

This research was supported by Grant #9507884S from the Oklahoma Affiliate of the American Heart Association, and by Grant HD38019 from NIH.

References (38)

  • C.S Trop et al.

    Autonomic dysreflexia and its urological implications: a review

    J. Urol.

    (1991)
  • R.W Blair et al.

    Spinal expression of Fos to colorectal distension is enhanced 30 days, but not 1 day, after spinal transection

    Soc. Neurosci. Abst.

    (1998)
  • E Bullitt

    Expression of c-fos-like protein as a marker for neuronal activity following noxious stimulation in the rat

    J. Comp. Neurol.

    (1990)
  • C.-L Cheng et al.

    Effect of capsaicin on the micturition reflex in normal and chronic spinal cord-injured cats

    Am. J. Physiol.

    (1999)
  • K Chung et al.

    Spinal projections of pelvic visceral afferents of the rat: a calcitonin gene-related peptide (CGRP) immunohistochemical study

    J. Comp. Neurol.

    (1993)
  • Hebel, R., Stromberg, M.W., 1986. Anatomy and Embryology of the Laboratory Rat. BioMed Verlag, Wörthsee, pp....
  • S.F Hobbs et al.

    Cardiac and abdominal vagal afferent inhibition of primate T9–S1 spinothalamic cells

    Am. J. Physiol.

    (1989)
  • C.N Honda

    Visceral and somatic afferent convergence onto neurons near the central canal in the sacral spinal cord of the cat

    J. Neurophysiol.

    (1985)
  • S.P Hunt et al.

    Induction of c-fos-like protein in spinal cord neurons following sensory stimulation

    Nature

    (1987)
  • Cited by (24)

    • Combining Constitutively Active Rheb Expression and Chondroitinase Promotes Functional Axonal Regeneration after Cervical Spinal Cord Injury

      2017, Molecular Therapy
      Citation Excerpt :

      In our previous studies, we were able to assess synapse formation by placing the PNG bridge that lies outside the spinal cord on a hook electrode to specifically stimulate regenerating axons within the graft. We and others have used the immediate-early gene c-Fos as a marker of transsynaptic neuronal activation.10,13,26,27 We counted the number of c-Fos neurons in host spinal cord after electrical stimulation of the PNG as an indicator of neurons that were synapsed upon by axons that grew out of the PNG.

    • The pattern of Fos expression in the spinal dorsal horn following acute noxious mechanical stimulation of bone

      2008, European Journal of Pain
      Citation Excerpt :

      Fos expression is greatest in the superficial dorsal horn following brief noxious mechanical stimulation of cutaneous tissues (Dai et al., 2001; Jinks et al., 2002a; Jinks et al., 2002b; Leah et al., 1992; Rahman et al., 2002; Shimode et al., 2003). In contrast, Fos expression is greatest in the deep dorsal horn following noxious mechanical stimulation of visceral tissues (Birder and de Groat, 1992; Birder and de Groat, 1993; Cruz et al., 1994; Ghanima et al., 2002; Ghanima et al., 2000; Landrum et al., 2002; Tong et al., 2003; Traub and Murphy, 2002; Traub et al., 1995; Traub et al., 2002). This highlights the notion that spinal mechanisms that mediate pain of cutaneous and visceral origin are different.

    View all citing articles on Scopus
    View full text