Spinal nerve injury

Liu, C. N., Wall, R D., Ben-Dor, E., Michaelis, M., Amir, R., and Devor, M. (2000). Tactile allodynia in the absence of C-fiber activation Altered firing properties of DRG neurons following spinal nerve injury. Pain 85, 503-521. 

Zhou XF, Deng YS, Xian CJ, Zhong JH (2000) Neurotrophins from dorsal root ganglia trigger allodynia after spinal nerve injury in rats. Eur J Neurosci 12 100-105... 

Deng Y S, Zhong J H, Zhou X F (2000). Effects of endogenous neurotrophins on sympathetic sprouting in the dorsal root ganglia and allodynia following spinal nerve injury. Exper. Neurol. 164 344-350. 

Zhang J, De Koninck Y (2006) Spatial and temporal relationship between monocyte chemoattractant protein-1 expression and spinal glial activation following peripheral nerve injury. J Neurochem 97 772-783... 

An intriguing area of research on opioids has been the accumulating evidence for plasticity in opioid controls. The degree of effectiveness of morphine analgesia is snbject to modulation by other transmitter systems in the spinal cord and by pathological changes induced by peripheral nerve injury. Thus in neuropathic states, pain after nerve injury, morphine analgesia can be reduced (but can still be effective) and tactics other than dose-escalation to circumvent this will be briefly discussed in Chapter 21. 

Association of Pain, neuropathic pain is defined as pain initiated or caused by a primary lesion, dysfunction in the nervous system". Neuropathy can be divided broadly into peripheral and central neuropathic pain, depending on whether the primary lesion or dysfunction is situated in the peripheral or central nervous system. In the periphery, neuropathic pain can result from disease or inflammatory states that affect peripheral nerves (e.g. diabetes mellitus, herpes zoster, HIV) or alternatively due to neuroma formation (amputation, nerve transection), nerve compression (e.g. tumours, entrapment) or other injuries (e.g. nerve crush, trauma). Central pain syndromes, on the other hand, result from alterations in different regions of the brain or the spinal cord. Examples include tumour or trauma affecting particular CNS structures (e.g. brainstem and thalamus) or spinal cord injury. Both the symptoms and origins of neuropathic pain are extremely diverse. Due to this variability, neuropathic pain syndromes are often difficult to treat. Some of the clinical symptoms associated with this condition include spontaneous pain, tactile allodynia (touch-evoked pain), hyperalgesia (enhanced responses to a painful stimulus) and sensory deficits. 

People with any condition that can compromise respiratory function or the handling of respiratory secretions (i.e., a condition that makes it hard to breathe or swallow, such as brain injury or disease, spinal cord injuries, seizure disorders, or other nerve or muscle disorders)... 

Polyradiculopathy Disease or injury involving multiple spinal nerve roots. 

A broad variety of diseases may cause neuropathic pain 935 Injured axons may develop spontaneous and repetitive firing known as ectopic activity 935 Sensory neurons transform their phenotype 936 Spinal disinhibition allows more nociceptive signal input 936 Peripheral nerve injury provokes a marked neuroimmune reaction 937... 

Spinal disinhibition allows more nociceptive signal input. Following peripheral nerve injury there is a reduction in the GABAergic component of postsynaptic inhibitory currents caused by a degeneration of GABAergic interneurons [24] (Fig. 57-6). This loss of inhibition (disinhibition) results in an overall increase in the excitability of dorsal horn neurons. The degeneration of inhibitory interneurons is due to an excitotoxic effect of primary afferent ectopic activity on dorsal horn neurons [26]. 

Moore, K. A. et al. Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. /. Neurosci. 22 6724-6731, 2002. 

Tsuda, M. et al. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature424 778-783, 2003. 

Causes of organic ED include diseases that compromise vascular flow to the corpora cavernosum (e.g., peripheral vascular disease, arteriosclerosis, essential hypertension), impair nerve conduction to the brain (e.g., spinal cord injury, stroke), and are associated with hypogonadism (e.g., prostate or testicular cancer, hypothalamic or pituitary disorders). 

Other nerve structures are also subject to variation. The position in the vertebral column at which the spinal cord terminates varies over three full vertebrae, and no standard terminal position exists. The positions at which various nerves enter the spinal cord likewise vary from individual to individual. About 15 per cent of the population do not have a "direct pyramidal" nerve tract in the spinal cord. Most human beings have 31 pairs of spinal nerves corresponding to 30 vertebrae some, however, have 32 and some 33 pairs, corresponding to 31 and 32 vertebrae, respectively. Most people have two splanchnic nerves (sympathetic nerves to the digestive system), but occasional individuals have three. In some individuals the sciatic nerve is so embedded that it is always fully protected in others, the pathway of the nerve is such that injury is very likely to occur. 

Chaplan SR, Malmberg AB, Yaksh TL (1997) Efficacy of spinal NMDA receptor antagonism in formalin hyperalgesia and nerve injury evoked aUodynia in the rat. J Pharmacol Exp Ther 280 829-838... 

Cummins, T. R. and Waxman, S. G. Downregulation of tetrodotoxin- resistant sodium currents and up-regulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neruons after nerve injury, J. Neurosci. 1997, 17, 3503-3514. 

Compounds with moderate p-affinities are very potent in a variety of pain models in mice and rats. In addition to antinociceptive efficacy in models of acute pain (tail flick, writhing) these compounds inhibit acute and persistent inflammatory pain (Randall Selitto, formalin test). Furthermore, they show strong inhibition of acute visceral pain (colorectal distension) and of tactile and cold allodynia in models of neuropathic pain (spinal nerve ligation (Chung), chronic constriction injury (Bennett)). The data suggest these compounds to be potential candidates for the management of clinical pain indications. Somatic and visceral pain with and without inflammatory conditions as well as neuropathic pain might be addressed with this approach. 

Mao, J., Price, D. D., Mayer, D. J.,Hayes, R. L. Pain-related increases in spinal cord membrane-bound proteinkinase C following peripheral nerve injury, Brain Res. 1992, 588, 144-149. 

Fundytus, M. E., Yashpal, K., Chabot, J.-G., Osborne, M. G., Lefebvre, C. D., Dray, A., Henry, J. L., Coderre, T. J. Knockdown of spinal metabotropic glutamate receptor 1 (mGluRI) alleviates pain and restores opioid efficacy after nerve injury in rats, Br. J. Pharmacol. 2001, 132, 354-367. 

Further experimental evidence for the involvement of SP in pain perception came from knock-out animals. Mice, in which the preprotachykinin A gene was disrupted, showed significantly reduced responses in tests that involved more intense noxious stimuli (Cao et al., 1998). De Felipe et al. (1998) disrupted the N receptor, and found the characteristic amplification ( wind up ) and intensity coding of nociceptive reflexes to be absent. NK receptor knockout mice show no changes in acute nociception tests. In contrast, SP and NKi receptor knock-out mice show reduction in responses to inflammatory stimuli. Nerve injury-induced mechanical but not thermal hyperalgesia is attenuated in NKi receptor knock-out mice, when inducing chronic neuropathic pain by unilateral ligation of the L5 spinal nerve (Mansikka et al., 2000). 

Chung model of neuropathic pain Nerve injury in rats is induced by a tight ligation of the root of the spinal nerve at L5-L6. Animals show hyperalgesia and allodynia similar to the Bennet model. Tactile allodynia, measured with von Frey hairs, is the most reliable parameter of pain intensity in this model (Kim and Chung, Pain 1992, 50, 355-363). 

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