**1. Introduction**

A lesion or disease affecting the somatosensory system can cause a wide range of pathophy‐ siologic symptoms including mild or severe chronic pain. Due to the diversity of etiologies giving rise to nervous system damage that generates neuropathic pain, it has become a ubiquitous health concern without respect for geographic or socioeconomic boundaries [1]. Within the developing world, infectious diseases [2-4] and trauma [5] are the most common sources of neuropathic pain syndromes. The developed world, in contrast, suffers more frequently from diabetic polyneuropathy (DPN) [6, 7], post herpetic neuralgia (PHN) from herpes zoster infections [8], and chemotherapy-induced peripheral neuropathy (CIPN) [9, 10]. There is relatively little epidemiological data regarding the prevalence of neuropathic pain within the general population, but a few estimates suggest it is around 7-8% [11, 12]. Despite the widespread occurrence of neuropathic pain, treatment options are limited and often ineffective, leaving many to live with the persistent agony and psychosocial burden associated with chronic pain [13, 14].

Neuropathic pain can present as on-going or spontaneous discomfort that occurs in the absence of any observable stimulus or a painful hypersensitivity to temperature and touch. This limits physical capabilities and impairs emotional well-being, often interfering with an individual's ability to earn a living or maintain healthy relationships. It is not surprising, therefore, that people with chronic pain have increased incidence of anxiety and depression and reduced scores in quantitative measures of health related quality of life [15].

Despite significant progress in chronic and neuropathic pain research, which has led to the discovery of several efficacious treatments in rodent models, pain management in humans

© 2013 Ramirez et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

remains ineffective and insufficient [16]. The lack of translational efficiency may be due to inadequate animal models that do not faithfully recapitulate human disease or from biological differences between rodents and humans [16]. Whatever the cause, the translational gap necessitates a bridge between clinicians and basic researchers in order to move from the clinic to the laboratory and back into the clinic.

measurable sensory abnormalities into underlying pathology. With a clear view of mecha‐

Neuropathic Pain: From Mechanism to Clinical Application

http://dx.doi.org/10.5772/55277

5

At the turn of the 20th century Charles Sherrington proposed the concept of pain-specific neural circuitry and deemed neurons within this circuit "nociceptors" [22]. This "specificity theory" of pain was competing for favor with the prevailing "pattern theory" which held that pain was encoded by the same low-threshold sensory nerve endings that transmit information about vibration and light touch through high frequency stimulation and central summation [23]. It is now clear, as Sherrington proposed that the sensation of pain is encoded by a unique set of peripheral and central neurons whose primary purpose is to alert the organism to a potentially

The nociceptive system detects noxious stimuli (i.e. that are of a sufficient magnitude to cause bodily injury) and elicits appropriate avoidance behaviors. Detection begins with free nerve endings in the skin or viscera that carry specialized membrane receptors capable of converting high magnitude chemical, mechanical, or thermal energy into an electrical impulse. The impulse is carried from the periphery to the dorsal horn of the spinal cord where neurotrans‐ mitter release relays the activity to second order neurons. Here, signals from the periphery are integrated with information from descending sources that modulate nociceptive circuitry in a manner that is dependent on the environmental context. The sum of this exchange is carried by secondary projection neurons to supraspinal nuclei which interpret the signal and create

The nociceptive circuit is not static, however; there is tremendous plasticity, from the periphery to the neocortex, which modulates the perception of pain to reflect the physiological needs of the organism and optimize survival. This is best understood by considering two examples of hypo- and hyper- sensitivity to pain: a time of war and an illness, respectively. Perceiving pain during a period of intense stress, such as wartime, would decrease chances of survival by increasing vulnerability to a more immediate threat. Conversely, in a low stress environment activation of the inflammatory response as a result of illness or injury sensitizes nociceptors leading to pain hypersensitivity, rest, and healing. Neuropathic pain, therefore, can be considered an inappropriate hijacking of inherent neuronal plasticity to promote hypersensi‐

Noxious stimuli are perceived by small diameter peripheral neurons whose free nerve endings are distributed throughout the body. These neurons are distinct from, although anatomically proximal to, the low threshold mechanoreceptors responsible for the perception of vibration and light touch. Both low and high threshold afferents are pseudounipolar neurons of the

nism, targeted treatment and individualized medicine become conceivable.

**3. Anatomical overview of pain as a somatosensory modality**

dangerous situation.

the conscious perception of pain.

tivity in contexts where it is not beneficial.

**4. Peripheral nociceptors detect a noxious stimulus**

In an attempt to increase the efficacy of medical treatment for neuropathic pain, clinicians and researchers have been moving away from an etiology based classification towards one that is mechanism based. It is current practice to diagnose a person who presents with neuropathic pain according to the underlying etiology and lesion topography [17]. However, this does not translate to effective patient care as these classification criteria do not suggest efficacious treatment. A more apt diagnosis might include a description of symptoms and the underlying pathophysiology associated with those symptoms. This chapter attempts to define neuropathic pain at the cellular and molecular level, as seen by a laboratory scientist, and then describe how the manifestations of these pathophysiologic changes are observed in the clinic, as seen by a clinician. It will then discuss a merger of the two points of view and suggest how this can lead to better patient care through more effective treatment.
