Tendons such as the Achilles tendon are complex structures that are hypocel
lular, hypovascular, and hyponeural, The development of pathophysiologic fu
nction in this tendon because of overuse is relatively common; however, the
mechanisms responsible for the development of paratenonitis and tendinosis
remain primarily undefined. To understand better a possible regulatory rol
e for neuropeptides (substance P and calcitonin gene related peptide) known
to be present in this tissue, the influence of substance P and calcitonin
gene related peptide on messenger ribonucleic acid levels for numerous infl
ammatory molecules, growth factors, and proteinases and inhibitors have bee
n assessed using a semiquantitative reverse transcription-polymerase chain
reaction method and explants of paratenon and Achilles tendon midsubstance
tissue from adolescent male and female rabbits and tissue from primigravida
females. Most of the significant (p < 0.01) changes observed were at the l
evel of the growth factor transcripts and transcripts for proteinases and i
nhibitors. Twenty-one significant differences in the responsiveness between
tissues from male and female rabbits were observed, and 12 significant dif
ferences in responsiveness between virgin females and primigravida rabbits
were seen. Differences between paratenon and: midsubstance responsiveness t
o the neuropeptides also were observed within each group of animals. The mi
dsubstance tissue from pregnant animals was hyporesponsive to both neuropep
tides. These results indicate that neurotransmitter responsiveness of Achil
les tendon tissue differs in a gender specific manner and is influenced by
pregnancy associated factors.