Effects of aging on primary afferent function
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Pain in the elderly people is often under-reported that leads to inadequate analgesia, slower recovery and poorer ambulation and function. The decreased pain sensitivity after aging is considered to be responsible for this but underlying mechanisms are not clear. A fundamental gap exists in our understanding whether structural, neurochemical, and molecular changes in the primary afferents lead to functional abnormalities, which contribute to the diminished pain sensitivity after aging. The long-term goal is to better understand mechanisms involved in age-related diminished pain sensitivity. The objective of this application is to determine how age-related changes in primary afferents affect normal pain sensitivity. The central hypothesis of this application is that primary afferent terminals located in the epidermis are decreased in number and that such changes affect pain related behaviors and the ability of afferents to encode natural stimuli. The rationale for the proposed research is that, once it is known that aged subjects have defective function of afferents, the clinician will predict a greater level of underlying pathology when elderly people make a report of pain. Thus, the proposed research is relevant to that part of NIA¿s mission that pertains to promote research to develop new or improved approaches for disease and disability detection and diagnosis. Guided by our preliminary data in the young animals, our central hypothesis will be tested by pursuing the following three Specific Aims: 1) Identify age-related changes in epidermal innervation that affect primary afferent function; 2) Determine whether aging causes alteration of the conduction velocity of primary afferents and their ability to respond to mechanical, heat and cold stimuli; and 3) Determine whether age-related changes in epidermal innervation and primary afferent function influence pain-related behaviors. Under the first specific aim, we will use a double immunolabelling technique to quantify the density of epidermal nerves in the young, adult and aged rats. Under the second specific aim, we will use skin-nerve in vitro preparation to record the activity of single primary afferent axons innervating same tissues (glabrous part of hind paw skin) as used in specific aim #1. Under the third specific aim, heat pain, cold sensation, and tactile threshold related behaviors will be evaluated. The approach is innovative, because it capitalizes on a new means of identifying changes in the functionality of afferents. The proposal takes advantage of single nerve fiber recording procedures in vitro, which to our knowledge is available in only a few laboratories in the USA. The successful completion of this project will have an important positive impact, because the identified functional anomalies of afferents are expected to provide knowledge about the effect of aging on functions of the pain pathway. In addition, it is expected that such an accomplishment will fundamentally advance our current level of understanding of pain mechanisms related to aging. Public health relevance: The proposed studies are of an important and under-investigated area of aging research that has potential applicability to understanding functional abnormalities of pain receptors located in the skin surface and underlying causes for such abnormalities. The research has significance to public health, because it will identify why age-related decreases in pain sensitivity are observed in many clinical studies. Thus, the findings are ultimately expected to be applicable to develop a unique pain management strategy for elderly people.
