| 1. |
- Jongsma, Helen, et al.
(författare)
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Markedly reduced chronic nociceptive response in mice lacking the PAC1 receptor
- 2001
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Ingår i: NeuroReport. - 1473-558X. ; 12:10, s. 2215-2219
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) has been proposed to have a role in nociception. Here we have used the formalin test, thermal laser stimulation and mechanical von Frey stimulation to investigate possible alteration of PAC1-/- mice nociceptive behaviour. Our finding, that PAC1-/- mice have a substantial, 75% decrease in nociceptive response during the late phase, provides clear evidence that the specific PACAP-receptor PAC1 is involved in the mediation of nociceptive responses during chronic conditions such as inflammation. PAC1-/- mice had small or no changes in the response to mechanical and thermal laser stimulation. This suggests a limited, if any, involvement of PAC1 in nociception after short-lasting stimuli. Injury-induced changes in DRG neuropeptide expression were more pronounced in PAC1-/- mice, implying neuroregulatory functions of PAC1.
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| 2. |
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| 3. |
- Jongsma Wallin, Helen, et al.
(författare)
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Exogenous NT-3 and NGF differentially modulate PACAP expression in adult sensory neurons, suggesting distinct roles in injury and inflammation
- 2001
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 14:2, s. 267-282
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Tidskriftsartikel (refereegranskat)abstract
- Expression of pituitary adenylate cyclase-activating polypeptide in sensory neurons varies with injury or inflammation. The neurotrophins NGF and NT-3 are profound regulators of neuronal peptidergic phenotype in intact and injured sensory neurons. This study examined their potential for modulation of PACAP expression in adult rat with intact and injured L4-L6 spinal nerves with or without immediate or delayed intrathecal infusion of NT-3 or NGF. Results indicate that in L5 DRG, few trkC neurons express high levels of PACAP mRNA in the intact state, but many do following injury. The elevated expression in injured neurons is mitigated by NT-3 infusion, suggesting a role for NT-3 in returning the 'injured phenotype' back towards an 'Intact phenotype'. NGF dramatically up-regulated PACAP expression in trkA-positive neurons in both intact and injured DRGs, implicating NGF as a positive regulator of PACAP expression in nociceptive neurons. Surprisingly, NT-3 modulates PACAP expression in an antagonistic fashion to NGF in intact neurons, an effect most evident in the trkA neurons not expressing trkC. Both NT-3 and NGF infusion results in decreased detection of PACAP protein in the region of the gracile nuclei, where central axons of the peripherally axotomized large sensory fibers terminate. NGF infusion also greatly increased the amount of PACAP protein detected in the portion of the dorsal horn innervated by small-medium size DRG neurons, while both neurotrophins appear able to prevent the decrease in PACAP expression observed in these afferents with injury. These results provide the first insights into the potential molecules implicated in the complex regulation of PACAP expression in sensory neurons.
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| 4. |
- Kerns, JM, et al.
(författare)
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A comparison of peripheral nerve regeneration in acellular muscle and nerve autografts
- 2003
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 37:4, s. 193-200
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Tidskriftsartikel (refereegranskat)abstract
- Regeneration of the rat sciatic nerve through acellular muscle and nerve autografts was evaluated 6-28 days postoperatively by the sensory pinch test, immunocytochemical staining for neurofilaments, and light and electron microscopy. Data points generated by the pinch test were plotted against postoperative time periods and by the use of regression analysis the initial delay period for muscle grafts was determined to 10.3 days. This value was similar to that previously published for acellular nerve grafts (9.5 days), but significantly longer than that for fresh nerve grafts (3.6 days). The calculated regeneration rate (slope of the regression line) for muscle grafts (1.8 mm/day) did not differ significantly ( p >0.05) from that calculated for acellular nerve grafts (2.1 mm/day) or for fresh nerve grafts (1.5 mm/day). The front of regenerating axons shown by axonal neurofilament staining confirmed the pinch test results. Both types of acellular grafts were repopulated with host non-neuronal cells and the muscle graft contained occasional ectopic muscle fibres. Remnants of graft basal laminae were evident at the ultrastructural level. These results indicate the suitability of either acellular muscle or nerve grafts for nerve repair despite their prolonged initial delay periods compared with conventional fresh nerve grafts.
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| 5. |
- Kerns, James, et al.
(författare)
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Effects of gradual bone lengthening on the rabbit tibial nerve
- 2001
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 35:4, s. 361-368
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the effect of gradual bone lengthening on peripheral nerves. In the present study, an external fixation device was applied to the rabbit tibia, which was then divided. After seven days, the tibia was subjected to 0.7 mm/day callus distraction for periods of up to one month. The tibial nerve was fixed in glutaraldehyde and plastic sections were cut in longitudinal and transverse planes for light and electron microscopy. Light microscopy showed a 64% increase in the gap length at the node of Ranvier in myelinated axons from the experimental side compared with the control side. The cross-sectional area of the non-myelinated axons was not altered significantly. We conclude that gradual stretching of the nerve elongates the nerve fibres at least at the region of the nodes, perhaps a point of least resistance. Diameters of fibres seem to be held more constant during the lengthening procedure.
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| 6. |
- Kvist, Martin, et al.
(författare)
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Effects of FK506 on regeneration and macrophages in injured rat sciatic nerve.
- 2003
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1085-9489 .- 1529-8027. ; 8:4, s. 251-259
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Tidskriftsartikel (refereegranskat)abstract
- Effects of FK506 [5.0 mg/kg body weight (BW), subcutaneous, daily] on nerve regeneration and presence of macrophages in lesioned rat sciatic nerves were studied. Models of autologous nerve graft or a nerve crush lesion were used and regeneration was evaluated by immunocytochemistry (also used to detect ED1/ED2 macrophages) and sensory pinch reflex test, respectively. Treatment with FK506 did not increase regeneration distance or regeneration rate in the autologous nerve grafts. However, regeneration distances after nerve crush were significantly longer following treatment with FK506. The number of macrophages (ED1/ED2) in nerve grafts increased over time, but treatment with FK506 had limited effects only in the presence of ED2 macrophages. Present and previously published studies may imply that there is a time-related and type-of-injury-related profile of FK506's pro-regenerative effect.
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| 7. |
- Pettersson, Lina, et al.
(författare)
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Changes in expression of PACAP in rat sensory neurons in response to sciatic nerve compression.
- 2004
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 20:7, s. 1838-1848
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, expression of pituitary adenylate cyclase-activating polypeptide (PACAP) in rat dorsal root ganglion (DRG) neurons and sciatic nerve following experimental sciatic nerve compression was studied with the use of quantitative immunohistochemistry and in situ hybridization. Previously, we have investigated changes in PACAP expression after nerve transection and, here, the far more frequently encountered condition of nerve compression injury is examined. Nerve compression was performed unilaterally on the rat sciatic nerve, at mid-thigh level, by application of a narrow silicone tube around the nerve for 3, 7, 14 or 28 days, respectively. We detect a statistically significant upregulation in the number and density of PACAP mRNA expression in both small and large DRG neurons in response to nerve compression. An increased number of PACAP-immunoreactive neurons is also found in the ipsilateral DRG. In addition, PACAP immunoreactivity is observed in the compressed sciatic nerve segment and adjacent nerve tissue after nerve compression. The present findings can be compared with previous studies where we have shown that PACAP expression is upregulated in DRG; in response to peripheral inflammation (primarily in small-medium neurons), and after axotomy (dramatic upregulation in medium-large neurons). In view of the recent findings of an increased PACAP expression in DRG after nerve compression, as well as the previous findings of a modulation of PACAP expression in response to axotomy and inflammation, it is likely that PACAP is also involved in the modulation of the response to peripheral nerve compression.
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| 8. |
- Pettersson, Lina, et al.
(författare)
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Expression of orphanin FQ/nociceptin and its receptor in rat peripheral ganglia and spinal cord.
- 2002
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Ingår i: Brain Research. - 1872-6240. ; 945:2, s. 266-275
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Tidskriftsartikel (refereegranskat)abstract
- Expression of the neuropeptide orphanin FQ/nociceptin (OFQ/N) and its receptor, the opioid receptor-like receptor (ORL1), have been found to have a wide distribution in the central nervous system, and in brain areas involved in sensory perception in particular. The effects of OFQ/N on, e.g., sensory transmission are very complex, and a modulatory effect on pain perception has been suggested. We therefore wanted to investigate the distribution of OFQ/N and ORL1 in the spinal cord and DRG, and also in SCG and some other peripheral tissues. The methods used were in situ hybridization, immunohistochemistry and ligand binding. We found that OFQ/N and ORL1 mRNA are expressed in DRG; primarily in small and large neurons, respectively. In spinal cord, mRNA for OFQ/N and ORL1 is expressed in neurons in laminae I, II and X, and in ventral horn neurons. Further, immunoreactivity for OFQ/N is observed in fibers and neurons in the superficial laminae of the dorsal horn and around the central canal, and also in neurons in the ventral horn of the spinal cord. Receptor ligand binding to the spinal cord grey matter is demonstrated, primarily concentrated to the dorsal horn and around the central canal, and also to medium and large size DRG neurons. These findings on the morphological distribution pattern of OFQ/N and ORL1 at the cellular level may support the notion that OFQ/N is involved in modulating pain transmission. Further, expression of OFQ/N and ORL1 mRNA was also found in SCG, whereas expression was undetectable in skin.
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| 9. |
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| 10. |
- Rosengren, Agneta, et al.
(författare)
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Tissue reactions evoked by porous and plane surfaces made out of silicon and titanium.
- 2002
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Ingår i: IEEE Transactions on Biomedical Engineering. - : Institute of Electrical and Electronics Engineers (IEEE). - 1558-2531 .- 0018-9294. ; 49:4, s. 392-399
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Tidskriftsartikel (refereegranskat)abstract
- Square-shaped silicon or titanium implants with plane or porous surfaces surrounded by a rim of silicone were implanted in the rat abdominal wall for evaluation of the tissue response after one, six, or 12 weeks. Cell damage was identified as increased membrane permeability using fluorescence microscopy by injection of propidium iodide prior to the killing of the rats. Capsule thickness and immunohistochemical quantification of macrophages were used as a further measure of the foreign-body reaction. There were no significant differences in capsular cell densities for macrophages, total cells (macrophages, fibroblasts, and other cells), or necrotic cells at the different time points for the four surfaces studied. However, significant differences in the kinetics of the response were found between plane surfaces compared with porous ones. Both types of plane surfaces developed a significant increase in capsule thickness over time in contrast to the porous implants. Porous silicon displayed a significant decrease in total cells in the reactive capsule over time. Furthermore, porous silicon and titanium surfaces displayed a significant decrease in total cell numbers at the implant interface between six and 12 weeks. The present study demonstrated that implanted silicon elicited soft-tissue reactions comparable to that of titanium
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