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Featured researches published by Johan Wallin.


European Journal of Pain | 2002

Gabapentin and pregabalin suppress tactile allodynia and potentiate spinal cord stimulation in a model of neuropathy

Johan Wallin; Jian-Guo Cui; Vadim Yakhnitsa; Gastón Schechtmann; Björn A. Meyerson; Bengt Linderoth

Spinal cord stimulation (SCS) is an effective tool in alleviating neuropathic pain. However, a number of well‐selected patients fail to obtain satisfactory pain relief. Previous studies have demonstrated that i.t. baclofen and/or adenosine can enhance the SCS effect, but this combined therapy has been shown to be useful in less than half of the cases and more effective substances are therefore needed. The aim of this experimental study in rats was to examine whether gabapentin or pregabalin attenuates tactile allodynia following partial sciatic nerve injury and whether subeffective doses of these drugs can potentiate the effects of SCS in rats which do not respond to SCS. Mononeuropathy was produced by a photochemically induced ischaemic lesion of the sciatic nerve. Tactile withdrawal thresholds were assessed with von Frey filaments. Effects of increasing doses of gabapentin and pregabalin (i.t. and i.v.) on the withdrawal thresholds were analysed. These drugs were found to reduce tactile allodynia in a dose‐dependent manner. In SCS non‐responding rats, i.e. where stimulation per se failed to suppress allodynia, a combination of SCS and subeffective doses of the drugs markedly attenuated allodynia. In subsequent acute experiments, extracellular recordings from wide dynamic range neurones in the dorsal horn showed prominent hyperexcitability. The combination of SCS and gabapentin, at the same subeffective dose, clearly enhanced suppression of this hyperexcitability. In conclusion, electrical therapy and pharmacological therapy in neuropathic pain can, when they are inefficient individually, become effective when combined.


Human Immunology | 1987

HLA-DR-DQ haplotypes defined by restriction fragment analysis: Correlation to serology

B. Carlsson; Johan Wallin; J. Böhme; Erna Möller

Through the analysis of RFLP (restriction fragment length polymorphism) of the HLA-DR beta, -DQ alpha, and -DQ beta genes from 70 serologically well-characterized individuals, we have established unique HLA-DR-DQ RFLP haplotypes correlating to all of the DR1-w14 specificities. The RFLP of DR beta, DQ alpha, and DQ beta genes is very high using the restriction enzyme TaqI and 21 DR-DQ RFLP haplotypes were defined with this restriction enzyme. Our analysis confirms the strong linkage disequilibrium between alleles in the DR and DQ loci. DR beta RFLP indicates a common ancestor for the DR alleles within either of the supertypic DRw52 and DRw53 specificities. The DQ beta gene shows a high degree of RFLP, and the RFLP alleles partly reflect the serologic DQw1-w3 specificities. The results presented here also demonstrate the heterogeneity of DRw6 (DRw13 and DRw14) associated haplotypes, and the DRw13 related Dw18 and Dw19 specificities were found to have distinct DR-DQ haplotypes. The DQw1 positive haplotypes DR1, 2, w10, w13, and w14 are related with regard to DQ alpha and DQ beta RFLPs and the DRw52 positive haplotypes DR3, w11, and w12, as well as the DRw53 positive haplotypes DR4, 7, and w9, are related with regard to DR beta and DQ alpha RFLPs. These findings indicate that polymorphic sequences around the DQ alpha gene are associated with DR beta and DQ beta polymorphism, which suggests a location of the DQ alpha gene between DR beta and DQ beta.


Immunogenetics | 1990

Different HLA DR-DQ associations in subgroups of idiopathic myasthenia gravis.

B. Carlsson; Johan Wallin; Ritva Pirskanen; Georg Matell; C. I. Edvard Smith

We have investigated theHLA-DRB and -DQB gene polymorphism in 131 myasthenia gravis (MG) patients. TheHLA genotypes in these patients were assigned by means of restriction fragment length polymorphism (RFLP)-definedDR-DQ haplotypes, correlating to serologic HLA class II typing. Using this technique we could, among randomly selected non-thymomatous (NT)-MG patients, confirm the strong association to DR3, and 70% of the patients were found to carry a specific DR3-positiveDR-DQ haplotype,T-3.1. Furthermore, an analysis of T-3.1− NT-MG patients revealed that 59 % were T-4.1÷ (DR4, DQw8). Thymic hyperplasia was found in approximately 85 % of the T-3.1+ , as well as of the T-4.1+ /3.1− patients. As previously observed, we found a clear dominance of females among the T-3.1+ NT-MG patients. However, among T-4.1+/3.1- patients, males were as common as females. Furthermore, the T-4.1+ patients were significantly older at the onset of disease than those who were T-3.1+. In female MG patients, the DRwl5-Dw2-positive haplotypeT-2.1 was strongly correlated with the presence of thymoma (T-MG). These data indicate that the HLA associations in early vs late onset of NT-MG are different, and that female patients with and without thymoma differ from each other with regard to HLA markers. Thus, at least three different HLA DR-DQ associations are found in subgroups of idiopathic MG.


Anesthesia & Analgesia | 2004

Intrathecal Clonidine Potentiates Suppression of Tactile Hypersensitivity by Spinal Cord Stimulation in a Model of Neuropathy

Gastón Schechtmann; Johan Wallin; Björn A. Meyerson; Bengt Linderoth

Spinal cord stimulation (SCS) may provide pain relief in approximately 60%–70% of well selected patients with pain caused by peripheral nerve injury. We have previously demonstrated that intrathecal (IT) administration of small doses of certain drugs, both in experimental animals and in patients, significantly enhances the pain-relieving effect of SCS. The &agr;2-adrenoceptor agonist, clonidine, is extensively used as an adjunct to spinal morphine and is suggested to be particularly effective for neuropathic pain, but its clinical use is limited by side effects such as sedation and hypotension. In this study, we investigated the dose-response characteristics of IT clonidine, and whether a subeffective dose of clonidine could enhance the effect of SCS in nerve-injured rats with tactile hypersensitivity (allodynia). Results showed that clonidine, in doses of 1–20 μg, reduced the hypersensitivity in a dose-dependent manner. In rats in which SCS per se failed to suppress tactile hypersensitivity, the combination of SCS and a subeffective dose of clonidine appeared to be highly synergistic and markedly attenuated the hypersensitivity. These results suggest that small doses of IT clonidine may be combined with SCS in neuropathic pain patients who do not obtain satisfactory relief with SCS alone.


Brain Research | 2003

Spinal cord stimulation inhibits long-term potentiation of spinal wide dynamic range neurons.

Johan Wallin; Atle Fiskå; Arne Tjølsen; Bengt Linderoth; Kjell Hole

It has been suggested that long-term potentiation (LTP) of dorsal horn neurons is a phenomenon that contributes to the development of chronic neuropathic pain. Spinal cord stimulation (SCS) may be an effective tool in alleviating such pain. The aim of this electrophysiological study in rats was to examine if SCS suppresses LTP of dorsal horn wide dynamic range (WDR) neurons. Increased knowledge of the mechanisms behind the effects of SCS may facilitate its further advancement and improve clinical efficacy. As previously shown, intensive, high-frequency electrical stimulation of the sciatic nerve in the rat induces an increased firing response of WDR neurons. Here we report that SCS gradually reduced this increased C-fiber response back to the baseline level. However, A-fiber responses were neither potentiated by the conditioning stimulus used nor were they affected by SCS. These data suggest that SCS affects the C-fiber component of dorsal horn central sensitization which is noteworthy since SCS, based on previous studies, is believed to primarily influence A-fiber functions.


Neuropeptides | 2002

Substance P release in the spinal dorsal horn following peripheral nerve injury

Johan Wallin; E. Schött

Spinal microdialysis was used to study the potassium induced in vivo release of substance P (SP) in the rat dorsal horn at different time points (3, 14, and 60 days) following partial sciatic nerve ligation (PNL) or sciatic nerve axotomy. The withdrawal threshold to innocuous mechanical stimuli was investigated with von Frey filaments in the PNL rats prior to microdialysis. The release of SP was significantly elevated at 60 days following PNL but not following complete nerve injury. However, the PNL rats in all time groups displayed mechanical hypersensitivity, which implies that this late change in SP release seems to be unrelated to the development of neuropathy. The present results indicate that there is an increase of the releasable pool of SP in the dorsal horn at late post-operative times after PNL. This change in SP release may reflect an altered sensory processing or may instead relate to adaptive responses to promote recovery.


Archive | 1984

HLA Class II Polymorphism: Restriction Fragment Patterns Correlated to Ninth Workshop Serology and Function

Johan Wallin; Jan Böhme; B. Carlsson; Erna Möller; Per A. Peterson; L. Rask

Recent studies have vastly expanded our knowledge of MHC gene organization and structure [for review see 6, 7, 13]. The HLA class II gene map is presently thought to contain at least three DRβ, one DRα, two DQβ two DQα, two DPβ and two DPα genes. Serological studies indicate at least four distinct class II antigens: DR, supertypic DR (DRw52, w53), DQ and DP [12; for review see 10]. It is now possible to isolate HLA class II cDNA and genomic clones with recombinant DNA techniques. With the use of cDNA specific for DRβ, DQβ and DQα and a genomic clone corresponding to an DPβ chain first domain as probes in genomic hybridizations, we have investigated the class II gene polymorphism. The cDNA and genomic clones used as probes are described elsewhere for DRβ [1], DQβ [8], DQα [3], and DPβ (K. Gustafsson, unpublished results). As the HLA glycoproteins retain their antigenic specificities even in the absence of carbohydrate moieties [11], it can be expected that all biologically relevant polymorphism can be detected at the DNA level.


Annals of the New York Academy of Sciences | 1987

Analysis of HLA DR and DQ β‐Genes in Myasthenia Gravis Patientsa

C. I. Edvard Smith; B. Carlsson; Lennart Hammarström; Georg Matell; Erna Möller; Ritva Pirskanen; Johan Wallin

In 1972 it was first reported that myasthenia gravis is associated with an increased frequency of certain HLA-antigens.’ The association has been further analyzed by a number of investigators, and certain patterns have emerged. Thus, the spontaneous form occurring mainly in young females (but also when it occurs in young males) is associated with the serological specificities HLA-BS/DR3*.’ as well as HLA-Dw3.’ In individuals with late onset of disease, as well as in patients with a concomitant thymoma the picture is less clear?” In peaicillamine-induced disease Bw35/DRl is increased.‘ Since the analysis of restriction fragment length polymorphism displayed by DR and DQ genes can be used for HLA-typing,’ we wanted to use this method to further analyze the association in myasthenia gravis.


Annals of the New York Academy of Sciences | 1988

Polymorphism of HLA Class II Genes in Various Diseases

Erna Möller; B. Carlsson; Olle Olerup; Johan Wallin

Many diseases are associated with genes of the HLA region. Several disease associations were described before class I1 genes were known, such as ankylosing spondylitis to HLA-B27 and psoriasis vulgaris to HL.4-Bl3, 17, and 37. Knowledge of the B27 association is now almost complete. In our material as well as in the data of the 1980 Histocompatibility Workshop, all patients with ankylosing spondylitis or pelvospondylitis ossificans are B27 positive. B27-negative patients with pelvospondylitis seem to have a different disease as the basis for their spondylitis. In contrast, psoriasis vulgaris is now more closely associated with Cw6 and DR7, alleles that are in linkage disequilibrium with B13, 17, and 37. Similarly, insulin-dependent diabetes mellitus (IDDM) was first associated with HLA-B8 and 15 and later more closely asssociated with the cellular specificities Dw3 and w4 and the corresponding serologic specificities DR3 and 4.’ With the possibilities of also determining variation within the DQ locus using RFLP analysis and cDNA probes, the association with IDDM was found to be secondary to particular alleles of the DQ locus, referred to as DQPIV’ and DQw3.2 by Nepom et aL3 Todd et al.4 recently reported amino acid sequence analyses of DQ alleles known to be positively and negatively associated with IDDM and identified residue 57 in the DQB chain as a candidate responsible for IDDM susceptibility or resistance or both. To define the genes responsible for disease susceptibility, it is imperative to have methods of resolving the relevant level of genomic variability of genes that determine T-cell repertoire and serve as restricting elements for T-cell recognition. Genes of the HLA-D region were first detected by cellular methods and typing in MLR using homozygous typing cells. Later, when class I1 products were shown to be present only on some lymphoid cells, serologic reagents that recognized class I1 antigens were selected. Names for such specificities, such as D Related-DR, were adopted to fit reactivities of these antibodies with HLA-D typed cell panels. At this time, D was thought to represent only one locus. Some DR specificities fit well with the adopted D terminology, such as Dwl and DR1 in Caucasoids, whereas others did not. As many as five distinct D specificities were all associated with serologic specificity DR4, named Dw4, 10, 13, 14, and 15. The DR7 group comprised cellular specificities Dw7, 11, and 17, and DR2 could be subdivided into Dw2, Dwl2, MN2 (= AZH) as well as cells with unknown D type (Dwx). When the polymorphic characters of the DQ locus were defined using biochemical, serologic, and molecular approaches, it became apparent that earlier defined D specificities were the total product of class I1 antigens expressed by the DR and the DQ IOCUS.~ Therefore, the D “alleles” were not true alleles of one locus, and the means of


Neuroscience Letters | 2006

Spinal NMDA receptor phosphorylation correlates with the presence of neuropathic signs following peripheral nerve injury in the rat

Camilla Ultenius; Bengt Linderoth; Björn A. Meyerson; Johan Wallin

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Gastón Schechtmann

Karolinska University Hospital

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