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Pain is influenced by many factors. The American Academy of Pediatrics along with the American Pain Society, Task Force on Pain in Infants, Children, and Adolescents emphasizes that, "Pain is an inherently subjective experience and should be assessed and treated as such. Pain has sensory, emotional, cognitive, and behavioral components that are interrelated with environmental, developmental, sociocultural, and contextual factors." 32 Pain is influenced by age, 33-35 race, 36 gender, 34, 35 and culture.37, 38

There are two categories of pain: Acute and chronic. Acute pain is usually associated with an injury or pathologic condition (i.e., sore throat) that generally resolves with the resolution of the inciting cause. Acute pain is mediated through nociceptors that fire in response to chemicals released during tissue damage, including leukotrienes, bradykinins, serotonin, histamine, and thromboxanes. Prostaglandins do not directly activate receptors; however, they act as a local mediator that enhances the sensitivity of the free nerve endings and produce pain and edema by their vasodilatory effect. 39 40 Nociceptors can be found in the skin, periosteum,  arterial walls, teeth, joint surfaces, and in the falx and tentorium of the cranial vault. 40 Nociceptors propagate their impulses through the peripheral nerve to their cell body in the dorsal horn of the spinal cord to the spinal cord where Substance P (a neurotransmitter) is released, which then relays the signal to the cortex via higher order neurons and the spinothalamic tract. Pain functions as a biologic alarm system to signify tissue damage and prevent further injury.

Additionally pain can be divided into somatic, visceral and neuropathic types. Noting the type of pain will help not only in making the diagnosis, but also in choosing the best therapy. Table 3, describes these types of pain, their mechanisms and effective therapies. Somatic pain is often seen in the ED and is straightforward.

Visceral pain is more complex and can be caused by ischemia, chemical stimulation and spasm, or overdistention of a hollow viscus.40 Afferent fibers from the affected organ converge on the same dorsal horn neurons as the somatic afferent fibers, which results in referred pain to the cutaneous area innervated at that level. Additionally, primary visceral pain afferents usually course along with autonomic nerve fibers. Thus, visceral pain is often accompanied by autonomic symptoms such as nausea, vomiting, hypotension, bradycardia, and sweating.

Neuropathic pain is initiated by an injury or dysfunction within the peripheral and/or central nervous system. Nociceptive and neuropathic pain can occur together. There are different types of pain that patients with neuropathic pain experience, see Table 4. In neuropathic pain, symptoms are initially experienced distal to the site of injury as opposed to nociceptive (somatic) pain, which is experienced at the site of injury or inflammation.

Reflex Sympathetic Dystrophy (RSD) or complex regional pain syndrome type I (CRPSI), is a pain syndrome thought to be of neuropathic origin. Given the complexity of this syndrome, the International Association for the Study of Pain (IASP) has introduced criteria for diagnostic purposes, see Table 5. Mechanisms that have been described to explain CRPS I include an excessive inflammatory response from peripheral sensitization and anincreased responsiveness to input at the level of the dorsal horn neurons from central sensitization. 41

Chronic pain is pain which lasts longer than would be expected for a given injury or pathologic condition. There are four types of pain seen in chronic pain conditions including: inflammatory, mechanical/compressive, neuropathic, and muscle dysfunction, see Table 6. Determining the mechanism involved can facilitate effective treatment. Remember that more than one mechanism can be involved in a given patient. 42

Approximately 50% of diabetics will develop neuropathy-related pain. Consequences of peripheral neuropathy in diabetics can be significant, including the development of a Charcot joint (hypertrophic arthropathy of the foot). Post-stroke neuropathic pain is seen in patients who develop pain in the same territory of the stroke. Skeletal muscle pain is a common cause of chronic pain and is a frequent diagnosis in pain clinics. Inflammatory pain involves inflammatory chemicals, e.g., prostaglandins, that directly stimulate the primary sensory nerves carrying pain information to the spinal cord. Mechanical or compressive pain is also a type of nociceptive pain in that mechanical pressure or stretching directly stimulates the pain sensitive neurons.

Early treatment of acute pain is important: repeated applications of noxious stimuli result in increased peripheral nociceptor responsiveness. A process known as "wind-up" occurs when there is a progressive increase in the output from dorsal horn neurons in response to repetitive inputs that are close together. This results in pain amplification. The initial response to a noxious stimulus is brief and causes a sharp, well-localized pain. Then, there is a more prolonged phase that is experienced as a dull, diffuse pain. A prolonged exposure to tissue injury can lead to sensitization of certain nerves in the pain pathways, which can lead to persistent pain after the initial condition has resolved.3 Beneficial symptom reduction may occur by preventing the initial neural cascade and thus eliminating the hypersensitivity produced by the noxious stimuli: This phenomenon has been named "preemptive analgesia." 43 44 The concept of preemptive analgesia has been studied in the context of post-operative pain management. A recent meta-analysis by Ong et al found that preemptive analgesia with epidural analgesia, local anesthesia, and NSAIDs resulted in consistent improvements in all three outcomes when results were combined for all three outcome measures (analgesic consumption, time to first rescue analgesic request, postoperative pain scores). 45


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