Pain in the elderly people is often under-reported that leads to inadequate analgesia, slowerrecovery and poorer ambulation and function. The decreased pain sensitivity after aging is considered to beresponsible for this but underlying mechanisms are not clear. A fundamental gap exists in ourunderstanding whether structural, neurochemical, and molecular changes in the primary afferents lead tofunctional abnormalities, which contribute to the diminished pain sensitivity after aging. The long-term goalis to better understand mechanisms involved in age-related diminished pain sensitivity. The objective of thisapplication is to determine how age-related changes in primary afferents affect normal pain sensitivity. Thecentral hypothesis of this application is that primary afferent terminals located in the epidermis aredecreased in number and that such changes affect pain related behaviors and the ability of afferents toencode natural stimuli. The rationale for the proposed research is that, once it is known that aged subjectshave defective function of afferents, the clinician will predict a greater level of underlying pathology whenelderly people make a report of pain. Thus, the proposed research is relevant to that part of NIA s missionthat pertains to promote research to develop new or improved approaches for disease and disabilitydetection and diagnosis. Guided by our preliminary data in the young animals, our central hypothesis will betested by pursuing the following three Specific Aims: 1) Identify age-related changes in epidermalinnervation that affect primary afferent function; 2) Determine whether aging causes alteration of theconduction velocity of primary afferents and their ability to respond to mechanical, heat and cold stimuli; and3) Determine whether age-related changes in epidermal innervation and primary afferent function influencepain-related behaviors. Under the first specific aim, we will use a double immunolabelling technique toquantify 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 innervatingsame tissues (glabrous part of hind paw skin) as used in specific aim #1. Under the third specific aim, heatpain, 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 proposaltakes advantage of single nerve fiber recording procedures in vitro, which to our knowledge is available inonly a few laboratories in the USA. The successful completion of this project will have an important positiveimpact, because the identified functional anomalies of afferents are expected to provide knowledge aboutthe effect of aging on functions of the pain pathway. In addition, it is expected that such an accomplishmentwill 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 potentialapplicability to understanding functional abnormalities of pain receptors located in the skin surface andunderlying causes for such abnormalities. The research has significance to public health, because it willidentify why age-related decreases in pain sensitivity are observed in many clinical studies. Thus, thefindings are ultimately expected to be applicable to develop a unique pain management strategy for elderlypeople.
| Kaliappan, Sankaranarayanan; Simone, Donald A; Banik, Ratan K (2018) Nonlinear Inverted-U Shaped Relationship Between Aging and Epidermal Innervation in the Rat Plantar Hind Paw: A Laser Scanning Confocal Microscopy Study. J Pain 19:1015-1023 |
| Kabadi, Rajiv; Kouya, Francois; Cohen, Hillel W et al. (2015) Spontaneous pain-like behaviors are more sensitive to morphine and buprenorphine than mechanically evoked behaviors in a rat model of acute postoperative pain. Anesth Analg 120:472-8 |
| Banik, Ratan K; Kabadi, Rajiv A (2013) A modified Hargreaves' method for assessing threshold temperatures for heat nociception. J Neurosci Methods 219:41-51 |
