Effect of peripheral nerve injury on cGMP and nitric oxide synthase levels in rat dorsal root ganglia: time course and coexistence.

Abstract

Using the indirect immunofluorescence method, the distribution of cyclic GMP (cGMP) and nitric oxide synthase (NOS) was investigated in lumbar 5 dorsal root ganglia (DRGs) of untreated rats 1, 3 and 7 days following sciatic nerve section (axotomy). Untreated and axotomized (7 days) rats were also studied after perfusion with the NO donor sodium nitroprusside (SNP). Moreover, rats were injected with carrageenan lambda into the unilateral hindpaw and studied after 6 h, 1 day or 2 days. An increase in the number of cGMP-positive satellite cell profiles was found in axotomized DRGs at 3 days with lower numbers after 7 days. In contrast, no change in cGMP-like immunoreactivity (LI) in satellite cell profiles was detected 1 day after axotomy or 6h, 1 day or 2 days after inflammation, as compared to controls. Axotomy induced a marked increase in the percentage of NOS-immunoreactive (IR) neuron profiles in the ipsilateral DRGs as follows: 3.0% at 1 day, 15% at 3 days and 25% at 7 days, whereas no significant change was found in the expression of NOS-LI in the inflamed DRGs as compared to untreated DRGs. Between 15 and 20% of all NOS-positive neuron profiles were surrounded by, or in partial contact with, cGMP-IR satellite cells in controls 1 and 3 days after axotomy, whereas the corresponding figure was around 5% after 7 days. After SNP perfusion 60-70% of all DRG neuron profiles were partly or totally associated with cGMP-positive satellite cell profiles, with no significant difference between untreated and axotomized ganglia. The nerve injury-induced, parallel upregulation of NOS in DRG neurons and cGMP in satellite cells in the initial phase after axotomy suggests an involvement of NO as a signalling molecule between neurons and satellite cells in DRGs, especially after peripheral nerve injury, perhaps exerting a survival effect as recently proposed by Thippeswamy and Morris (1997).