Biomedical subjects

C Sommer

Publications and source records attributed to C Sommer.

At least 55 records · Page 3Linked to original sources

PubMed2001

Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different mouse models of painful mononeuropathy.

We investigated the anti-hyperalgesic effect of neutralizing antibodies (AB) to tumor necrosis factor-alpha (TNF) in two murine models of neuropathy, the chronic constrictive sciatic nerve injury (CCI) which has a strong epineurial inflammatory component, and the partial sciatic nerve transection (PST), a 'pure' nerve injury model. In both models a single AB injection intra-operatively as well as on day 4 reduced thermal hyperalgesia significantly, whereas mechanical allodynia was only reduced with intraoperative but not with delayed treatment.

Animals↗

PubMed2001

Combined epineurial therapy with neutralizing antibodies to tumor necrosis factor-alpha and interleukin-1 receptor has an additive effect in reducing neuropathic pain in mice.

Monotherapy with antibodies to tumor necrosis factor-alpha (TNF) or interleukin-1 receptor 1 (IL-1R1) reduces hyperalgesia in an animal model of painful neuropathy. Here we investigated whether combined therapy with epineurial anti-TNF and anti-IL-1R1 antibodies produces a further advantage. C57BL/6 mice with a chronic constrictive injury of one sciatic nerve were treated epineurially with neutralizing antibodies to either IL-1R1 or TNF alone or with a combined application of neutralizing antibodies to TNF and IL-1R1. Combined treatment with anti-IL-1R1 and anti-TNF antibodies markedly reduced thermal hyperalgesia and mechanical allodynia more effectively than monotherapy with either antibody. There were no detectable differences in IL-1beta and TNF endoneurial protein expression between animals with monotherapy and combined treatment. We conclude that combined anti-cytokine therapy may be a useful strategy in the treatment of neuropathic pain.

Animals↗

PubMed2001

[Cytokines in neuropathic pain].

Cytokines are a heterogeneous group of polypeptides that were originally described to mediate activation of the immune system and inflammatory responses. Most of them have meanwhile been shown to be also produced by and act on the peripheral and central nervous system. There is ample evidence from experimental studies that proinflammatory cytokines induce or increase neuropathic pain as well as inflammatory pain. Direct actions of cytokines on afferent nerve fibers have been shown as well as actions involving further mediators such as prostaglandins or nerve growth factor. Inhibition of proinflammatory cytokines, either by synthesis inhibitors, inhibitors of cleavage from the cell membrane, by direct antagonists, or by anti-inflammatory antibodies, reduces pain and hyperalgesia in most models studied. Studies with cytokine knock-out animals often lead to different results from the pharmacological studies. This is in part due to compensatory mechanisms in the animals combined with the high redundancy of the cytokine system. Preliminary data from human studies are encouraging insofar as in the future, cytokine inhibition may add to the panel of treatment modalities for neuropathic pain.

Animals↗

PubMed2001

[Acute compartment syndrome. Results of a clinico-experimental study of pressure and time limits for emergency fasciotomy].

BACKGROUND: Acute compartment syndrome of the leg is to be regarded as a traumatological emergency. Most specialists already agree that only a timely operative decompression of the afflicted compartment can prevent serious tissue damage. What still remains subject to discussion, however, is the precise tissue pressure above which the operation becomes imperative. Experimental human studies focusing on tissue pressure and muscle oxygenation have not yet been carried out. It was thus the aim of the present study to analyze oxygen partial pressure of the anterior tibial muscle and peroneal action potential in a model compartment syndrome in man. METHODS: In 22 healthy, normotensive volunteers, constant pressure values from 0 to 100 mmHg were induced in the anterior tibial muscle with antishock trousers. Over a period of up to 6 h measurements were made of (1) tissue pressure, (2) intramuscular oxygen partial pressure (pO2), and (3) muscle response potential (MRP) of the n. peroneus profundus by electroneurography. RESULTS: We achieved a 97.7% (Q25%/Q75%: 89.2/99.8) transfer of the pneumatic pressure to the lower leg. Already at intramuscular tissue pressures of 30-40 mmHg, hypoxia and reduction of MRP appeared. A reduction of the MRP to zero and pO2 < 1 mmHg was observed from a pressure of 50 mmHg. Tissue pressure values of over 75 mmHg resulted almost without exception in anoxia of the muscle. CONCLUSIONS: Even under normal perfusion conditions, already slight increases in pressure of above 30 mmHg lead to reduced tissue oxygenation and neural function. We have to consider that with additionally traumatized muscle the ischemic tolerance is markedly reduced and due to unknown influences such as local vasoreactivity and capacity of autoregulation the nutritive perfusion cannot be determined. In the case of a severely injured muscle, to be on the safe side decompressive fasciotomy should therefore be carried out if pressure values remain above 30 mmHg.

Adult↗

PubMed2001

[Abdominal impalement injuries].

Impalement is an uncommon and spectacular injury, which combines aspects of both blunt and penetrating trauma. With reference to our own seven patients we discuss the initial management and the operative treatment of this rare injury. Further we demonstrate the imminent problems after impalement injuries such as removal of the impaled object, treatment of colon- and other abdominal organ injuries, and management of vascular injuries.

Abdominal Injuries↗

PubMed2001

[Acute disseminated encephalomyelitis (ADEM)].

Acute disseminated encephalomyelitis (ADEM) is an unusual demyelinating disease of the CNS. We review clinical symptoms, findings from radiological and CSF examinations, and current treatment strategies for ADEM. This disorder is often associated with a precedent infection or vaccination but may also occur spontaneously. The clinical symptoms are highly variable. Analysis of CSF usually reveals lymphocytic pleocytosis and an elevated protein content but may also yield normal results. Magnetic resonance imaging shows solitary or multiple lesions within the CNS. Most patients improve quickly with methylprednisolone. If that fails, immunoglobulin, plasmapheresis, or cytostatic drugs can be employed. Unlike MS, ADEM has a monophasic course and favourable long-term prognosis. Multiphasic courses are very rare. There are no diagnostic criteria to distinguish ADEM reliably from MS during the acute phase. We presume that ADEM is a variant of MS and not an independent disease entity.

Adult↗

PubMed2001

CT and MRI findings in gliomatosis cerebri: a neuroradiologic and neuropathologic review of diffuse infiltrating brain neoplasms.

The aim of the study was to develop objective criteria that might be helpful for the diagnosis of gliomatosis cerebri (GC) with the highest possible probability based on both the neuroradiological and histopathological findings. Imaging findings in 14 patients with diffuse infiltrating brain neoplasms were studied by two neuroradiologists. Computed tomography and MRI scans were compared with each other side by side. The extent and kind of disease were graded on a scale of 1-5. Interexamination agreement between the two methods was calculated using a kappa analysis. Neither of the neuroradiologists performed the examinations and both were blinded to the histopathological findings, which were also available for all patients, based on biopsy as well as follow-up CT and MRI studies. A neuroradiological-neuropathological correlation was performed. A score system helped to differentiate the findings in three categories: 1 = suggestive of GC; 2 = GC cannot be excluded; and 3 = others. Both CT and MRI were performed in 14 patients with clinical signs and symptoms of an intracerebral tumor. All examinations had diagnostic quality and showed the involvement of at least two brain lobes. Stereotactic biopsy was carried out in all patients. In 2 patients the neuropathological diagnosis was suggestive of GC, in 1 patient glioblastoma, in 2 patients astrocytoma, and in 5 patients nonspecific astrogliotic proliferation. In the remaining 4 cases anaplastic tumor infiltration was diagnosed. The neuroradiological findings in 5 cases were suggestive of GC; in 6 cases a GC could not excluded; and in 3 patients only a slight probability of GC was found. In 2 cases was the neuropathological and the neuroradiological diagnosis of GC concordant. Magnetic resonance imaging is significantly more sensitive than CT in the diagnosis of GC. However, even with multiple, MRI-guided stereotactic biopsies in correlation with intraoperative analysis of the sample by smear preparations by a neuropathologist the antemortem diagnosis of GC is still difficult. Discussion of neuropathological and neuroradiological findings in each case in combination with a score system may help to resolve discrepancies.

Adolescent↗

PubMed2001

Kainate-induced epilepsy alters protein expression of AMPA receptor subunits GluR1, GluR2 and AMPA receptor binding protein in the rat hippocampus.

Kainic acid induces seizures with consecutive degeneration of highly vulnerable hippocampal CA3 neurons in adult rats. An abnormal influx of calcium through newly synthesized alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptors lacking the GluR2 subunit, which normally renders AMPA receptors calcium impermeable, is thought to play a pivotal role for postictal neuronal death (GluR2 hypothesis). Using a specific GluR2 antiserum, postictal hippocampal GluR2 protein expression was investigated and compared to GluR1 between 6 and 96 h after seizure induction. In addition, postictal protein expression of a recently cloned AMPA receptor binding protein (ABP), which anchors AMPA receptors in the plasma membrane was also analyzed, to address the question of whether its protein expression is associated with neuronal death or survival. At 6 h after seizure induction, GluR2 immunoreactivity (IR) in CA3 was more markedly reduced compared to GluR1, but at 24 h GluR2 IR reattained control levels. More importantly, GluR2 IR was also markedly, but transiently decreased between 6 and 48 h in hippocampal CA1 neurons, but no significant cell loss was observed. These findings modify the GluR2 hypothesis in so far as only a subset of, but not all, hippocampal CA1 and CA3 pyramidal neurons may die due to reduced GluR2 levels with consecutive calcium overload through calcium-permeable AMPA receptors. ABP was induced postictally in presumed CA2 and a subpopulation of CA3 neurons and seems not to be involved in mechanisms of delayed neuronal death.

Animals↗

PubMed2001

[Distal radius fractures--retrospective quality control after conservative and operative therapy].

BACKGROUND: The distal radius fracture is the most frequent fracture in the adult patient. The wide spectrum of different types of fracture and the coexisting factors make the choice for the optimal treatment difficult. As an interne quality control we retrospectively evaluated all patients with distal radius fractures treated in 1995 at our institution. METHODS: The study included 69 adult patients with 71 distal radius fractures. After on average 26 months 58 patients with 59 fractures were clinically and radiologically evaluated. The patients were asked to give supplementary information about their follow-up treatment as well as any remaining physical difficulties and limitations in the daily life. All x-rays of the broken radius were carefully analysed and compared with the opposite side. The final results were evaluated according to the "Demerit Point System". RESULTS: Patients were treated with five different therapeutical methods. 76.3% of the patients showed a very good/good final result. In 56.7% of the cases secondary fracture dislocation occurred; the dislocation-rate of fractures treated with percutaneous k-wires was 93.3%! A clear correlation between secondary displacement and final results was found. CONCLUSION: A main factor for an optimal outcome is the anatomic restoration of length and axis of the distal radius as well as of joint congruency, also moderate angular deformities are well tolerated. Our collective showed an unexpected high rate of secondary displacement, especially in the k-wire group. The reasons for this unsatisfactory event are manifold: too optimistic indication, insufficient follow-up examination in the first four to six weeks, inconsequent change to a more stable fixation method in case of a secondary dislocation. The results of this retrospective evaluation had a major impact on our concept of treatment. The dorso-radial double-plate technique combined with bone graft will be more used in the future especially in younger patients. The new standardised concept is the base of a present prospective study.

Adolescent↗

PubMed2001

Etanercept reduces hyperalgesia in experimental painful neuropathy.

Etanercept, a recombinant tumor necrosis factor receptor (p75)-Fc fusion protein competitively inhibits tumor necrosis factor-alpha (TNF). Etanercept has been successfully used in patients with rheumatoid arthritis, where it reduces pain and inflammation. Because locally produced proinflammatory cytokines play a role in pain after nerve injury, we investigated whether etanercept can reduce pain and hyperalgesia in an animal model of painful neuropathy, the chronic constriction injury of the sciatic nerve. C57BL/6 mice received etanercept or sham treatment by local near-nerve injection to the injured nerve or by systemic application. Treatment with etanercept reduced thermal hyperalgesia and mechanical allodynia significantly in both modes of application. The effect of etanercept was present in animals that were treated from the time of surgery and in those that were treated from day 6, when hyperalgesia was already present. These results suggest the potential of etanercept as a treatment option for patients with neuropathic pain.

Animals↗

PubMed2001

Expression of synaptopodin, an actin-associated protein, in the rat hippocampus after limbic epilepsy.

Synaptopodin, a 100 kD protein, associated with the actin cytoskeleton of the postsynaptic density and dendritic spines, is thought to play a role in modulating actin-based shape and motility of dendritic spines during formation or elimination of synaptic contacts. Temporal lobe epilepsy in humans and in rats shows neuronal damage, aberrant sprouting of hippocampal mossy fibers and subsequent synaptic remodeling processes. Using kainic acid (KA) induced epilepsy in rats, the postictal hippocampal expression of synaptopodin was analyzed by in situ hybridization (ISH) and immunohistochemistry. Sprouting of mossy fibers was visualized by a modified Timm's staining. ISH showed elevated levels of Synaptopodin mRNA in perikarya of CA3 principal neurons, dentate granule cells and in surviving hilar neurons these levels persisted up to 8 weeks after seizure induction. Synaptopodin immunoreactivity in the dendritic layers of CA3, in the hilus and in the inner molecular layer of the dentate gyrus (DG) was initially reduced. Eight weeks after KA treatment Synaptopodin protein expression returned to control levels in dendritic layers of CA3 and in the entire molecular layer of the DG. The recovery of protein expression was accompanied by simultaneous supra- and infragranular mossy fiber sprouting. Postictal upregulation of Synaptopodin mRNA levels in target cell populations of limbic epilepsy-elicited damage and subsequent Synaptopodin protein expression largely co-localized with remodeling processes as demonstrated by mossy fiber sprouting. It may thus represent a novel postsynaptic molecular correlate of hippocampal neuroplasticity.

Animals↗

PubMed2001

Delayed neuroprotective effect of insulin-like growth factor-i after experimental transient focal cerebral ischemia monitored with mri.

BACKGROUND AND PURPOSE: Insulin-like growth factor (IGF) treatment has been shown to have trophic and neuroprotective effects in vitro and in vivo in different lesion models. IGF-I has potent neuroprotective effects after hypoxic-ischemic injury and global ischemia. The role of IGF-I in focal cerebral ischemia is only partially understood. Therefore, in the present study, we evaluated, by applying MRI monitoring, whether a clinically relevant systemic administration of IGF-I can achieve a long-lasting neuroprotective effect. METHODS: Male Wistar rats underwent transient occlusion of the right middle cerebral artery for 1 hour by using the suture occlusion model. Animals then were intraventricularly treated with 33.33 microg IGF-I/d for 3 days (group A, the IGF-I group [n=13]; group B, the placebo group [n=14]) or subcutaneously treated with 200 microg IGF-I/d for 7 days (group D, the IGF-I group [n=10]; group E, the placebo group [n=10]). Groups C and F served as sham-operated controls (n=5 and n=3, respectively). Treatment was begun 30 minutes after occlusion of the middle cerebral artery. Subcutaneously treated animals underwent MRI studies (diffusion-weighted imaging, perfusion imaging, and T2-weighted imaging) beginning 60 minutes after vessel occlusion at 6 hours and at days 1, 2, 5, and 7 after ischemia. The animals were weighed and neurologically assessed daily (rating scale ranged from 0, indicating no deficit, to 5, indicating death). On the third day (intraventricular trial) and on the seventh day (subcutaneous trial), animals were euthanized, and brain sections were stained with triphenyltetrazolium chloride. RESULTS: The mean infarct volume was 52.9+/-25.2 mm(3) in intraventricularly treated animals versus 146.4+/-62.2 mm(3) in control animals (P<0.01) and 42.2+/-17.9 mm(3) in subcutaneously IGF-I-treated animals versus 73.1+/-38.1 mm(3) in control animals (P<0.05). Apparent diffusion coefficient-derived lesion volume at 60 minutes after occlusion was 40.4+/-23.7 mm(3) versus 38.3+/-19.3 mm(3) (P=NS), increased to 168.3+/-49.55 mm(3) versus 105.5+/-33.8 mm(3) (P<0.05) at 24 hours, and then decreased to 55.8+/-30.3 mm(3) versus 23.3+/-20.2 mm(3) (P<0.05) for control and IGF-I-treated animals, respectively. The T2-weighted-derived ischemic lesion volume at 24 hours after occlusion was 236+/-49.2 mm(3) versus 115.9+/-56.8 mm(3) (P<0.05) and decreased to 115.9+/-26.2 mm(3) versus 75.7+/-35.8 mm(3) (P<0.05) at day 7 for control and IGF-I-treated animals, respectively. The relative regional cerebral blood volume was reduced to 50% before reperfusion in all regions of interest except for region of interest 1 (vessel territory of anterior cerebral artery), recovered during reperfusion, but was not different between the control and the growth factor-treated group at any imaging time point. There was no significant difference in weight loss. There was less neurological deficit after ischemia in intraventricularly and subcutaneously IGF-I-treated animals compared with control animals (P<0.05). CONCLUSIONS: Continuous treatment with intraventricularly and subcutaneously administered IGF-I achieved a long-lasting neuroprotective effect as early as 24 hours after ischemia as measured by MRI. Therefore, IGF-I may represent a new approach to the treatment of focal cerebral ischemia.

Animals↗

PubMed2001

Protein S-100B: a serum marker for ischemic and infectious injury of cerebral tissue.

The S-100B protein is released by injured astrocytes. After passage through a disintegrated blood-brain barrier (BBB) the molecule can be detected in the peripheral circulation. We investigated the association between the extent of brain injury and S-100B concentration in serum in cerebral injury caused by cerebral ischemia and cerebral fungal infection. Study I: The S-100B serum concentration was serially determined in 24 patients with ischemic stroke at 4, 8, 10, 24, 72 hours after the onset of symptoms. We observed that patients with brain lesions larger than 5 cm3 exhibited significantly increased serum levels of S-100B at 10, 24 and 72 hours compared to those with lesion volumes below 5 cm3. Furthermore, an association between S-100B serum concentration and neurological outcome was observed. Study II: In a mouse model of systemic fungal infection with Candida albicans we observed that serum levels of S-100B increased at day 1 after intravenous infection. At this time we could histologically demonstrate brain tissue injury by invading hyphae which had crossed the BBB. Furthermore, reactive astrogliosis was demonstrated by immunohistochemistry. On day 7 we found a significant decrease of S-100B serum level compared to day 1 and 4. This was associated with a demarcation of the fungi with leukocytes in brain tissue at this late phase of infection. No further invasion through the BBB was seen on day 7. In conclusion, serum levels of S-100B reflect the time course of tissue injury in cerebral ischemia and cerebral infection to a similar extent. Thus, S-100B may be a useful marker to assess cerebral tissue injury.

Adult↗

PubMed2001

Topical treatment of calves with synthetic pyrethroids: effects on the non-target dung fly Neomyia cornicina (Diptera: Muscidae).

Dung from calves treated with synthetic pyrethroids negatively influenced, in varying degrees, survival, reproduction and size of the common dung fly Neomyia cornicina (Fabricius). This was documented in assays where the coprophagous larvae and adults of N. cornicina were exposed to dung collected from calves dosed with topical preparations of deltamethrin, flumethrin, cyfluthrin, and alpha-cypermethrin. Larval mortality was significantly increased in dung collected up to at least seven days after treatment with deltamethrin, alpha-cypermethrin and cyfluthrin. Alpha-cypermethrin caused significant mortality of adults allowed to feed on moist dung. Nulliparous flies fed for six days on dung collected three days after treatment of calves with alpha-cypermethrin or deltamethrin showed little or no ovarian development. A tendency for a comparable effect with flumethrin was also observed. A connection between ovarian development and inhibition of feeding was indicated by the observation of significantly lowered excretion rates in flies exposed to residues of deltamethrin, alpha-cypermethrin and flumethrin. Larvae that survived exposure to dung from calves dosed with deltamethrin, alpha-cypermethrin, or cyfluthrin gave rise to smaller flies. The effect on adult fly size decreased when larvae were exposed to dung collected at longer times after treatment of the calves. Adult fly size was significantly reduced in dung collected up to 14 days (alpha-cypermethrin) or up to 28 days after treatment (deltamethrin and cyfluthrin). Fluctuating asymmetry of a wing vein character did not reflect the anticipated levels of exposure. The study strongly indicated that the use of synthetic pyrethroids affected the insect dung fauna and that such use may reduce dung decomposition.

Animals↗

PubMed2001

Restricted diffusion within ring enhancement is not pathognomonic for brain abscess.

BACKGROUND AND PURPOSE: Recent experience suggests that diffusion-weighted MR imaging may be decisive in the differential diagnosis of ring-enhancing cerebral lesions. Whether restricted diffusion within a ring-enhancing cerebral mass lesion is pathognomonic for abscess was studied. METHODS: Seventeen patients with ring-enhancing cerebral lesions (three abscesses, six glioblastomas, eight metastases) on conventional contrast-enhanced T1-weighted images were examined with echo-planar diffusion-weighted MR imaging. Apparent diffusion coefficient (ADC) maps and the ADCs were calculated for all lesions. Lesions with signs of intralesional hemorrhage on unenhanced T1-weighted images were excluded. RESULTS: The central portion of all six glioblastomas and seven of eight metastases showed unrestricted diffusion, whereas two of three abscesses showed restricted diffusion (low ADC values) in their cavity. However, restricted diffusion also was found in one metastasis, and one abscess within a postoperative cavity showed unrestricted diffusion within a larger nondependent portion. CONCLUSION: In patients with ring-enhancing cerebral mass lesions, restricted diffusion might be characteristic but is not pathognomonic for abscess, as low ADC values also may be found in brain metastases.

Brain Abscess↗

PubMed2000

Temporary changes of the AP-1 transcription factor binding activity in the gerbil hippocampus after transient global ischemia, and ischemic tolerance induction.

Global forebrain ischemia of 5-min duration results in delayed neuronal death (DND) of CA1 neurons in the gerbil hippocampus. DND can be prevented by a preconditioning sublethal ischemic stimulus (2. 5 min), a phenomenon, known as ischemic tolerance induction. Striking evidence exists for the involvement of regulatory transcription factors encoded by immediate early genes (IEGs) in the fate of CA1 neurons. Here, we investigated by electrophoretic mobility shift assay (EMSA) the postischemic changes of the DNA binding activity of the Activator Protein-1 (AP-1) transcription factor complex after preconditioning, lethal ischemia, and after acquisition of an ischemic tolerant state. A short duration peak of AP-1 binding activity at 3 h of reperfusion was a hallmark of ischemic tolerance induction. The kinetics of this activation profile, i.e. the rapid linear increase between 1 and 3 h and a similar rapid decline at 6 or 12 h of reperfusion are prominent within the CA1 and CA3 region of all ischemic groups which are designated for neuronal survival. No changes in the c-Jun and ATF-2 immunoreactivity were observed in the CA1 region, however an increase in only c-Jun immunoreactivity occurred in concordance with the elevation of AP-1 binding in the CA3 region. The results clearly demonstrate a differential regulation of AP-1 binding activity in CA1 during and after acquisition of an ischemic tolerant state in contrast to ischemia leading to neuronal death. The early peak at 3 h of reperfusion in AP-1 binding affinity observed in the single 2.5 min and the ischemic tolerant groups suggests a protective role of early AP-1 activation, whereas failure of this initial activation may contribute to DND. Our data furthermore suggest, that elevation of the AP-1 binding activity in the CA1 and CA3 regions underlies a different regulatory mechanism in the gerbil hippocampus after ischemic stress.

Animals↗

PubMed2000

Metabotropic glutamate receptor subtypes are differentially expressed after transient cerebral ischemia without, during and after tolerance induction in the gerbil hippocampus.

Postischemic delayed neuronal death (DND) of hippocampal CA1 neurons can be prevented by a preconditioning sublethal ischemic stimulus. To check for possible participation of metabotropic glutamate receptors (mGluRs) in neuronal death or survival, we analyzed postischemic protein expression of subtypes 1b and 5 of group I mGluRs, which are thought to exert neurotoxic effects after pathological activation due to ischemia, and subtypes 2 and 3 of group II mGluRs, which in contrast are thought to be neuroprotective in this state, respectively. Therefore, three groups of gerbils with reperfusion intervals between 8 h and 4 days (n=5 each) were investigated: one group was subjected to 5 min ischemia, resulting in DND of CA1 neurons, a second group to a tolerance inducing 2.5 min period of ischemia and a third group to 5 min ischemia after prior tolerance induction. The major finding was a transient postischemic reduction of mGluR1b and 5 expression in the ischemic tolerant CA1 subfield at 8 h. This downregulation of neurotoxic mGluRs may indicate a contribution to the survival of highly vulnerable CA1 neurons in the ischemic tolerant state.

Animals↗

PubMed2000

Effects of neutralizing antibodies to TNF-alpha on pain-related behavior and nerve regeneration in mice with chronic constriction injury.

Inhibition of proinflammatory cytokines reduces hyperalgesia in animal models of painful neuropathy. We set out to investigate the consequences of this treatment for nerve regeneration. Here we examined the sequels of epineurial application of neutralizing antibodies to tumor necrosis factor-alpha (TNF) in chronic constriction injury (CCI) of the sciatic nerve in C57/BL 6 mice. The mice were tested behaviorally for manifestations of thermal hyperalgesia and mechanical allodynia. Nerve regeneration was assessed by morphometry of myelinated nerve fibers in the sciatic nerve and of the epidermal innervation density in the glabrous skin of the hindpaws. Antibodies to TNF reduced thermal hyperalgesia and mechanical allodynia after CCI. Myelinated fiber density in the sciatic nerve was reduced to 30% of normal on day 7 after surgery, and reached 60% on day 45, with no difference between antibody-treated and untreated animals. Epidermal innervation density as shown by PGP 9.5 and CGRP immunohistochemistry was reduced to 25-47% at both time points after CCI, again without differences between antibody treated and untreated mice. Myelinated fiber density but not epidermal innervation density was correlated to thermal and mechanical withdrawal thresholds. We conclude that neutralization of endoneurial TNF attenuates pain related behavior but has no effect on nerve regeneration. Furthermore, the number of epidermal nerve fibers is not relevant to the magnitude of behavioral hyperalgesia in CCI.

Animals↗