Effects on the central and peripheral nervous systems

Pain initiates multiple plastic changes within the nervous system at peripheral, spinal, and supraspinal levels ( Coderre elal 1993; SGhaible,ยง.nd G..r.u..b.b 1993). Tissue injury increases sensitivity to stimuli that would not normally produce pain (allodynia), exaggerates responsiveness to noxious stimuli in the injured area (primary hyperalgesia), and leads to a spread of pain and hypersensitivity to uninjured adjacent areas (secondary hyperalgesia). These changes in sensitivity are caused by a reduction in nociceptive thresholds of large Ab sensory fibers (allodynia, secondary hyperalgesia) and thinly myelinated A and unmyelinated C fibers (primary and secondary hyperalgesia). Continuous nociceptive input from C and A fibers can trigger changes in the excitability of neurons in the spinal cord, which can persist even after the noxious stimulus has gone ('central sensitization') (Schaible.a.nd Giubb 1993). This sensitization of spinal cord neurons is reflected by increased spontaneous activity, increased responsiveness to afferent inputs ('wind up'), prolonged afterdischarges to repeated stimulation (persistent pain), and the expansion of the peripheral receptive fields of individual neurons ('central neuroplasticity').

The most distressing feature of these pathological processes is that they are associated with alterations in neuronal gene expression which outlast the primary nociceptive input and therefore may predispose to chronic pain ( Cod.erre.e.i.a.l 1993). A possible approach to preventing central sensitization after surgical trauma is to start adequate treatment of acute pain as early as possible, i.e. pre- or intraoperatively. This has led to the concept of 'pre-emptive analgesia'. The basic hypothesis is that analgesic treatment before the onset of a surgical trauma will be more effective than after surgery, when central sensitization has already been established. The practical value of this concept awaits further clinical studies ( Coderre eial 1993).

The pathological changes in the excitability of spinal neurons are initiated by the transmission of nociceptive stimuli in the dorsal horn of the spinal cord via release of neuropeptides or excitatory amino acids from primary afferent neurons. Neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP), and neurokinin A are clearly involved, and the synthesis and release of these substances is upregulated in the spinal cord after peripheral injury. Excitatory amino acids (glutamate, aspartate) are also released in the dorsal horn upon noxious stimulation; they activate postsynaptic N-methyl-D-aspartate (NMDA) and/or non-NMDA receptors and thereby facilitate the onset of central sensitization. Neuropeptides and excitatory amino acids trigger these alterations in membrane excitability through interactions with second-messenger systems such as intracellular calcium and protein kinases. Specific antagonists at neurokinin or NMDA receptors can effectively inhibit pain in animals (Coderre . et...al 1993; Schaible and Grubb .199.3).

Inhibitory mechanisms within the spinal cord are being activated to counteract hyperalgesia and pain. Animal models of inflammatory pain have demonstrated an increase in the production and release of endogenous morphine-like substances (enkephalins) in the spinal cord. These opioid peptides can activate either postsynaptic opioid receptors on spinal cord neurons or presynaptic opioid receptors on primary afferent neurons. Both these actions result in decreased excitabilities of the respective neurons and, in the latter case, a diminished release of excitatory neuropeptides or amino acids. Eventually, these actions lead to the inhibition of pain (Coderre . et... al 1993; Schaible _a_nd_G_r_ubb 1993).

Kicking Fear And Anxiety To The Curb

Kicking Fear And Anxiety To The Curb

Kicking Fear And Anxiety To The Curb Can Have Amazing Benefits For Your Life And Success. Learn About Calming Down And Gain Power By Learning Ways To Become Peaceful And Create Amazing Results.

Get My Free Ebook


Post a comment