Reduced sciatic nerve substance P and calcitonin gene-related peptide in rats with short-term diabetes or central hypoxaemia co-exist with normal messenger RNA levels in the lumbar dorsal root ganglia

Abstract

Endoneurial hypoxia of ischaemic origin is believed to cause the reduction in sciatic nerve substance P levels in experimentally diabetic rats. The first part of this study was designed to determine whether the changes seen extended to another neuropeptide, calcitonin gene-related peptide, and to reveal any correlation between substance P and calcitonin gene-related peptide levels in the sciatic nerve of both diabetic and centrally hypoxaemic rats. Comparison of streptozotocin diabetic rats (four-week duration) with their control group showed clear reductions in both substance P-like immunoreactivity (control= 225 ± 20pg/mg protein,diabetic= 139 ± 19; P < 0.01) and calcitonin gene-related peptide-like immunoreactivity (control= 9.08 ± 0.65ng/mg protein,diabetic= 4.43 ± 0.44; P < 0.001). A similar pattern was seen with the comparison of five-week centrally hypoxaemic rats (housed in 10% O 2) with their controls for both substance P-like immunoreactivity (control= 222 ± 10pg/mg protein,hypoxic= 148 ± 13; P < 0.001) and calcitonin gene-related peptide-like immunoreactivity (control= 6.58 ± 0.42ng/mg protein,hypoxic= 3.01 ± 0.45; P < 0.001). Calcitonin gene-related peptide levels correlated closely with substance P levels in both the diabetes and central hypoxaemia studies ( r 2 = 0.69 and 0.62, respectively). The second part of this study measured the messenger RNA levels of the substance P precursor, preprotachykinin-A, and calcitonin gene-related peptide messenger RNA in the L 4 and L 5 dorsal root ganglia of control, diabetic and centrally hypoxaemic rats. There was no change in preprotachykinin-A or calcitonin gene-related peptide messenger RNA levels between any of the groups, suggesting that the sciatic nerve decreases in substance P and calcitonin gene-related peptide described above are post-transcriptional in origin.