Systems neuroscienceTransient loss of terminals from non-peptidergic nociceptive fibers in the substantia gelatinosa of spinal cord following chronic constriction injury of the sciatic nerve
Section snippets
Experimental procedures
The guidelines contained in the Guide to the Care and Use of Experimental Animals of the Canadian Council on Animal Care, Volumes 1 and 2, were rigorously followed. Furthermore, all protocols were reviewed and approved by the McGill University Animal Care Committee before experimentation began. All measures were taken to minimize the number of animals used and their suffering.
Analysis of behavioral changes in sham-operated and neuropathic animals
Qualitative assessment of animal behavior following cuff application revealed that animals in the neuropathic group exhibited signs of nociceptive behavior including limping and guarding of the left (ipsilateral) hind paw. Guarding consisted of maintained withdrawal of the paw in an everted position with the toes together and slightly ventroflexed. Neuropathic animals exhibited signs of increased mechanical sensitivity at the 4g threshold by the 7th day following cuff application. This reached
Discussion
In this study, we confirmed that, following a chronic constriction injury of the sciatic nerve (CCI), there is a transient loss of IB4 binding in the dorsal horn of the spinal cord ipsilateral to the lesion. Furthermore, by expanding our study to the ultrastructural level, we were able to demonstrate that there was a bona fide loss of varicosities from non-peptidergic unmyelinated fibers, not simply a loss of binding sites, followed by an apparent restoration of the synaptic structure.
Conclusions
In this study, using a well-established neuropathic pain animal model, we detected for the first time a transient but selective loss of boutons from non-peptidergic nociceptive afferents which represent the central terminals of type I glomeruli in the spinal cord of these animals. The significance of these changes for the evolution of the pain is at present unclear, although they may play a role in the initial stages of the development of the hyperalgesia and allodynia.
It is also evident that
Acknowledgments
This research was support by CIHR grant #38093 to A. Ribeiro-da-Silva. Andrea Bailey acknowledges a studentship from the Louise Edwards Foundation. We are grateful to Gary J. Bennett and Véronique Kéna-Cohen for their help with the animal behavior, to Sid Parkinson for editorial assistance, and to Manon St. Louis, Vanessa Partridge and Johanne Ouellette for technical expertise.
References (50)
- et al.
GDNF rescues nonpeptidergic unmyelinated primary afferents in streptozotocin-treated diabetic mice
Exp Neurol
(2001) Neurotrophic factors and their receptors in human sensory neuropathies
Prog Brain Res
(2004)- et al.
Behavioural pain-related disorders and contribution of the saphenous nerve in crush and chronic constriction injury of the rat sciatic nerve
Pain
(1994) - et al.
Further evidence for ‘pain-related’ behaviours in a model of unilateral peripheral mononeuropathy
Pain
(1990) - et al.
Identification and ranking of genetic and laboratory environment factors influencing a behavioral trait, thermal nociception, via computational analysis of a large data archive
Neurosci Biobehav Rev
(2002) - et al.
Spared nerve injuryan animal model of persistent peripheral neuropathic pain
Pain
(2000) - et al.
Comparison of five different rat models of peripheral nerve injury
Pharmacol Biochem Behav
(2005) - et al.
A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia
Pain
(1988) - et al.
Expression of nerve growth factor in the dorsal root ganglion after peripheral nerve injury
Brain Res
(1998) - et al.
Partial sciatic nerve transection as a model of neuropathic paina qualitative and quantitative neuropathological study
Pain
(2000)
Differential pH and capsaicin responses of griffonia simplicifolia IB4 (IB4)-positive and IB4-negative small sensory neurons
Neuroscience
Noxious heat receptors present in cold-sensory cells in rats
Neurosci Lett
The effect of peripheral nerve section on lectin binding in the superficial dorsal horn of the rat spinal cord
Brain Res
Expression of lectin binding in the superficial dorsal horn of the rat spinal cord during pre- and postnatal development
Dev Brain Res
Substantia gelatinosa of the spinal cord
Expression of neurotrophin mRNAs in the dorsal root ganglion after spinal nerve injury
Mol Brain Res
Spared nerve injury model of neuropathic pain in the mousea behavioral and anatomic analysis
J Pain
Compensatory projection of primary nociceptors and c-fos induction in the spinal dorsal horn following neonatal sciatic nerve lesion
Exp Neurol
Neuropeptide expression in rat dorsal root ganglion cells and spinal cord after peripheral nerve injury with special reference to galanin
Neuroscience
Crossed-withdrawal reflex in a rat model of neuropathic painimplications in neural plasticity
Neurosci Lett
Nociceptors for the 21st century
Curr Rev Pain
Functional downregulation of P2X3 receptor subunit in rat sensory neurons reveals a significant role in chronic neuropathic and inflammatory pain
J Neurosci
Postnatal changes in the expression of the trkA high-affinity NGF receptor in primary sensory neurons
Eur J Neurosci
GAP-43 distribution is correlated with development of growth cones and presynaptic terminals
J Neurocytol
Time course of degenerative and regenerative changes in the dorsal horn in a rat model of peripheral neuropathy
J Comp Neurol
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