Faculty Bibliography

Cutaneous myelinated nociceptors are known to exhibit considerable heterogeneity in their response to noxious heat. In the present experiments, we studied heat sensitivity among myelinated nociceptors during early postnatal life to determine whether this heterogeneity is correlated with other physiological and anatomical properties. A total of 129 cutaneous myelinated nociceptors were recorded intracellularly and characterized using mechanical and thermal skin stimuli in ex vivo preparations from neonatal Swiss-Webster (SW) mice across postnatal ages P2-P10; physiologically identified cells were iontophoretically labeled with neurobiotin for analyses of dorsal horn terminations from heat-sensitive and heat-insensitive cells. Our results show that heat sensitivity is not strictly correlated with other physiological or anatomical properties, most notably mechanical threshold or laminar termination patterns, of myelinated nociceptors at these ages. Further, we found a marked decline in the number of heat-sensitive myelinated mechanonociceptors (A-mechanoheat nociceptors [AMHs]) during this early postnatal period. Indeed, 68% of myelinated nociceptors were AMHs between P2 and P5, whereas this percentage dropped to 36% between P6 and P10. Multiple independent lines of evidence suggest that this decrease reflects a change in phenotype in a subset of myelinated nociceptors that lose sensitivity to noxious heat in early postnatal life. Interestingly, evidence was also obtained for a significant strain difference since the early transient excess in the number of AMHs in P2-P5 SW neonates was not present in similarly aged neonates from the C57Bl/6 strain. Potential mechanisms underlying these postnatal changes in AMH number are discussed.

Ovulation is a prostaglandin (PG)-dependent process. Although n-3 polyunsaturated fatty acids (PUFA) and conjugated linoleic acid (CLA) have differing effects in the body, both reduce PG synthesis. We hypothesized that dietary n-3 fatty acids and CLA would differentially alter ovarian PG profiles through reductions in expression of enzymes involved in PG biosynthesis resulting in enhanced ovulation. Our objectives were to determine how dietary stearidonic acid and eicosapentaenoic acid (EPA) at 0.3 g/100 g diet and mixed isomers of CLA at 0.7 g/100 g diet, human achievable levels with daily consumption of fish or beef and dairy products, respectively, would influence ovulation and ovarian cyclooxygenase-1 (COX-1) and COX-2 expression in ovulation-induced rats. After 27 days on diet and ovulation induction, ovaries were isolated and analyzed from 22 pups per diet. Eicosapentaenoic acid ingestion reduced ova release by 16% while increasing PGE(2) and PGF(2alpha) release without altering COX-1 or COX-2 expression. Conversely, ovarian COX-1 expression was increased 135% with stearidonic acid ingestion associated with increased PGF(2alpha) without altering PGE(2) or ova release. Conjugated linoleic acid ingestion reduced COX-2 expression to 65% of that in rats consuming control and EPA diets; however, without affecting ovulation or PGs. Although it is generally believed that the COX-2 is the primary COX involved in ovulation, these results demonstrated that the n-3 PUFA differently affect ovarian COX-1 expression and that this effect differs from CLA, which reduced COX-2 expression. Further, although ovarian PGF(2alpha) is the primary PG altered by dietary n-3 PUFA, n-3 PUFA differentially influence ovarian PG biosynthesis and can decrease ova release, possibly induced through constitutive COX-1 enzyme expression.