Depletion of Endogenous Noradrenaline Does Not Prevent Spinal Cord Plasticity Following Peripheral Nerve Injury

Department of Anesthesiology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA.
The journal of pain: official journal of the American Pain Society (Impact Factor: 4.01). 12/2011; 13(1):49-57. DOI: 10.1016/j.jpain.2011.09.009
Source: PubMed


The present study examined the role of endogenous noradrenaline on glial and neuronal plasticity in the spinal cord in rats after peripheral nerve injury. An intrathecal injection of dopamine-β-hydroxylase antibody conjugated to saporin (DβH-saporin) completely depleted noradrenergic axons in the spinal cord and also reduced noradrenergic neurons in the locus coeruleus (A6) and A5 noradrenergic nucleus in the brainstem and noradrenergic axons in the paraventricular nucleus of the hypothalamus. DβH-saporin treatment itself did not alter mechanical withdrawal threshold, but enhanced mechanical hypersensitivity and intrathecal clonidine analgesia after L5-L6 spinal nerve ligation. In the spinal dorsal horn of spinal nerve ligation rats, DβH-saporin treatment increased choline acetyltransferase immunoreactivity as well as immunoreactivity in microglia of ionized calcium binding adaptor molecule 1[IBA1] and in astrocytes of glial fibrillary acidic protein, and brain-derived nerve growth factor content. DβH-saporin treatment did not, however, alter the fractional release of acetylcholine from terminals by dexmedetomidine after nerve injury. These results suggest that endogenous tone of noradrenergic fibers is not necessary for the plasticity of α2-adrenoceptor analgesia and glial activation after nerve injury, but might play an inhibitory role on glial activation. PERSPECTIVE: This study demonstrates that endogenous noradrenaline modulates plasticity of glia and cholinergic neurons in the spinal cord after peripheral nerve injury and hence influences the pathophysiology of spinal cord changes associated with neuropathic pain.

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    • "Postsynaptic stimulation of ␣ 2 adrenoceptors at the level of the spinal cord increases acetylcholine concentrations in the superficial dorsal horn and inhibits nociceptive neurotransmission by reducing the release of neurotransmitters such as substance P and glutamate [20] [40] [46] [78]. Spinal alpha 2 -adrenoceptor stimulation produces analgesia in animals with neuropathic pain, and this effect in animals is blocked by inhibition of brain-derived neurotrophic factor (BDNF) signaling pathway [33] [34] [35]. Dexmedetomidine can also inhibit glial cell hypertrophy in the spinal dorsal horn and activation of the extracellular signal-regulated kinase (ERK) signaling pathway [18] [43]. "
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    • "In turn, this inhibits the release of excitatory neurotransmitters from primary nociceptive afferents and blocks pain. The effectiveness of this anti-nociceptive mechanism sometimes strengthens following peripheral nerve injury (Ma and Eisenach, 2003; Hayashida et al., 2012). However, under certain conditions, this spinal anti-nociceptive influence may be compromised after peripheral nerve injury (Rahman et al., 2008), thereby contributing to pain. "
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