Female reproductive tract pain: targets, challenges, and outcomes

In order to deal effectively with danger, it is imperative to know about it. This is what nociceptors do--these primary sensory neurons are specialized to detect intense stimuli and represent, therefore, the first line of defense against any potentially threatening or damaging environmental inputs. By sensing noxious stimuli and contributing to the necessary reactions to avoid them--rapid withdrawal and the experience of an intensely unpleasant or painful sensation, nociceptors are essential for the maintenance of the body's integrity. Although nociceptive pain is clearly an adaptive alarm system, persistent pain is maladaptive, essentially an ongoing false alarm. Here, we highlight the genesis of nociceptors during development and the intrinsic properties of nociceptors that enable them to transduce, conduct, and transmit nociceptive information and also discuss how their phenotypic plasticity contributes to clinical pain.

To determine the prevalence of chronic pelvic pain in U.S. women aged 18-50 years, and to examine its association with health-related quality of life, work productivity, and health care utilization. In April and May 1994, the Gallup Organization telephoned 17,927 U.S. households to identify women aged 18-50 years who experienced chronic pelvic pain, ie, of at least 6 months' duration. Those who reported chronic pelvic pain were surveyed on severity, frequency, and diagnosis; quality of life; work loss and productivity; and health care utilization. Among 5263 eligible women who agreed to participate, 773 (14.7%) reported chronic pelvic pain within the past 3 months. Those who reported chronic pelvic pain had significantly lower mean scores for general health than those who did not (70.5 versus 78.8,P<.05), and 61% of those with chronic pelvic pain reported that the etiology was unknown. Women diagnosed with endometriosis reported the most health distress, pain during or after intercourse, and interference with activities because of pain. Estimated direct medical costs for outpatient visits for chronic pelvic pain for the U.S population of women aged 18-50 years are $881.5 million per year. Among 548 employed respondents, 15% reported time lost from paid work and 45% reported reduced work productivity. Frequently, the cause of chronic pain is undiagnosed, although it affects approximately one in seven U.S. women. Increased awareness of its cost and impact on quality of life should promote increased medical attention to this problem.

The highly disagreeable sensation of pain results from an extraordinarily complex and interactive series of mechanisms integrated at all levels of the neuroaxis, from the periphery, via the dorsal horn to higher cerebral structures. Pain is usually elicited by the activation of specific nociceptors ('nociceptive pain'). However, it may also result from injury to sensory fibres, or from damage to the CNS itself ('neuropathic pain'). Although acute and subchronic, nociceptive pain fulfils a warning role, chronic and/or severe nociceptive and neuropathic pain is maladaptive. Recent years have seen a progressive unravelling of the neuroanatomical circuits and cellular mechanisms underlying the induction of pain. In addition to familiar inflammatory mediators, such as prostaglandins and bradykinin, potentially-important, pronociceptive roles have been proposed for a variety of 'exotic' species, including protons, ATP, cytokines, neurotrophins (growth factors) and nitric oxide. Further, both in the periphery and in the CNS, non-neuronal glial and immunecompetent cells have been shown to play a modulatory role in the response to inflammation and injury, and in processes modifying nociception. In the dorsal horn of the spinal cord, wherein the primary processing of nociceptive information occurs, N-methyl-D-aspartate receptors are activated by glutamate released from nocisponsive afferent fibres. Their activation plays a key role in the induction of neuronal sensitization, a process underlying prolonged painful states. In addition, upon peripheral nerve injury, a reduction of inhibitory interneurone tone in the dorsal horn exacerbates sensitized states and further enhance nociception. As concerns the transfer of nociceptive information to the brain, several pathways other than the classical spinothalamic tract are of importance: for example, the postsynaptic dorsal column pathway. In discussing the roles of supraspinal structures in pain sensation, differences between its 'discriminative-sensory' and 'affective-cognitive' dimensions should be emphasized. The purpose of the present article is to provide a global account of mechanisms involved in the induction of pain. Particular attention is focused on cellular aspects and on the consequences of peripheral nerve injury. In the first part of the review, neuronal pathways for the transmission of nociceptive information from peripheral nerve terminals to the dorsal horn, and therefrom to higher centres, are outlined. This neuronal framework is then exploited for a consideration of peripheral, spinal and supraspinal mechanisms involved in the induction of pain by stimulation of peripheral nociceptors, by peripheral nerve injury and by damage to the CNS itself. Finally, a hypothesis is forwarded that neurotrophins may play an important role in central, adaptive mechanisms modulating nociception. An improved understanding of the origins of pain should facilitate the development of novel strategies for its more effective treatment.