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Regenerative medicine and other emerging chronic pain management (Proceedings)

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Nov 01, 2010

Accurate measurement of pain perception in individual non-human patients is impossible. However, management of pain requires objective measures of effectiveness of the applied treatment. This paradox of pain management underlies much of the frustration associated with clinical management of pain and creates the opportunity for ineffective treatments to be supported by "scientific" studies. As a veterinary care provider treating patients likely experiencing differing intensities of pain, it is important to understand the pros and cons of pain assessment methods and utilize a critical anthropomorphic evaluation and treatment of postoperative pain.

Critical anthropomorphic evaluation of pain
Animal behaviour differs between species, between individuals of the same species, and even within the same individual over time and with different environmental influences. Creating a rapid and simple method for evaluation of pain perception is unlikely. However many clinicians advocate the use of pain scoring to measure treatment effectiveness to prevent the unnecessary suffering of feline patients. The most useful approach to clinical treatment incorporates some of our own human experiences and feelings (anthropomorphic) but modifying those expected feelings based on knowledge of feline behaviour and physiology. While not scientifically rigorous, this critical anthropomorphic approach incorporates our knowledge of pain in humans with our understanding of how we expect animals to react to noxious stimulation to clinically guide our treatment of pain.

Pain Physiology
An important conceptual breakthrough in understanding pain physiology is the recognition that pain following most types of noxious stimulation is usually protective and quite distinct from pain resulting from overt damage to tissues or nerves. It plays an integral adaptive role as part of the body's normal defense mechanisms, warning of contact with potentially damaging environmental insults and initiating behavioral and reflex avoidance strategies. It is also often referred to as nociceptive pain because it is only elicited when intense noxious stimuli threaten to injure tissue. It is characterized by a high stimulus threshold, is well localized and transient, and demonstrates a stimulus-response relationship similar to the other somatosensations. This protective mechanism is facilitated by a highly specialized network of nociceptors and primary sensory neurons which encode the intensity, duration and quality of noxious stimuli and, by virtue of their topographically organized projections to the spinal cord, its location.

Nociception
The physiologic component of pain is termed nociception, which is comprised of the processes of transduction, transmission and modulation of neural signals generated in response to an external noxious stimulus. It is a physiologic process that, when carried to completion, results in the conscious perception of pain. In its simplest form the pain pathway can be considered as a three neuron chain, with the first order neuron originating in the periphery and projecting to the spinal cord, the second order neuron ascending the spinal cord, and the third order neuron projecting to the cerebral cortex. On a more complex level, the pathway involves a network of branches and communications with other sensory neurons and descending inhibitory neurons from the midbrain that modulate afferent transmission of painful stimuli.

Modulation of pain
The descending modulatory system has been described as having four tiers. The final, and perhaps most important, site involved in the descending modulation of nociceptive information is at the level of the spinal cord. Just as dorsal horn processing is vital to the integration of ascending noxious input, its role in anti-nociception is equally crucial. Dense concentrations of GABA, glycine, serotonin, norepinephrine and the endogenous opioid peptides (enkephalins, endorphins and dynorphins) have been identified in dorsal horn neurons, and all produce inhibitory effects on nociceptive transmission. Specifically, the spinal opioid system fine-tunes descending control mechanisms by acting both presynaptically, as well as postsynaptically. Communication among dorsal horn neurons involves complex interactions, and it is now apparent that a single neuron may be influenced by many neurotransmitters, that each neurotransmitter may have numerous actions in a given region, and that multiple neurotransmitters may exist within a single neuron. Simply stated on a more global level, nociceptive processing is a three-neuron chain with dual input at each level. Discriminative and affective aspects of pain are transmitted in related, and yet distinct ascending pathways, with modifications made by both segmental and descending modulatory systems.

Enhancement of nociceptive signals is of major concern in patients with chronic or neuropathic pain. Just as with inhibition, when signals are enhanced there are many points in the nociceptive pathways that can participate and are potential targets for intervention. It is important to remember that chronic pain is often multifaceted and involves several different mechanisms. Successful treatment may be extremely difficult in some cases. Resolution of the underlying disease is often the best strategy for curing chronic pain; however, in many situations chronic pain management is palliative and quality of life is a major consideration when treating these patients.