The Journal of Neurochemistry has retracted a 2008 paper, “Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury,” it had initially corrected — and how.
The correction, which appeared online in August 2010, was extensive:
We have previously reported that Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury (Obata et al. 2008). In the process of following up the findings in this paper, the authors found that the quantification graphs of RT-PCR cannot be reproduced from the existing data. Also the first 2 bands in Fig. 10 (Iba1 and IL-1β) were mistakenly created from an identical band. Therefore, we have newly started the setup of experiments by different experimenters to reproduce the results of RT-PCR since last September. We repeated the experiments twice and very unfortunately could not reproduce some results of RT-PCR.
We confirmed the increase in mRNAs in TLR3,4, Iba1, Il-1β, IL-6, TNF-α in spinal cord tissues of both rats received SNL surgery and poly I:C injection in Figs. 6, 10. However, our re-experiments could not reproduce the significant suppression of the gene expression. The effect of tube implantation into the subarachnoid space was too big to examine the antisense-oligo’s effect on the gene expression, and this failure may be because it has been performed by different experimenters. The exact reason of the difference from the original article is not clear. So far, we have found no significant evidence that the TLR3 antisense-oligo suppresses the induction of proinflammatory cytokines after nerve injury (Fig. 6) and poly I:C administration (Fig. 10). As a result, a part of the conclusion in this paper; “TLR3 has a role in the production of proinflammatory cytokines”, cannot be supported by the scientifically correct data. All authors sincerely regret this result and any inconveniences caused by this problem.
For starters, we’d like to think that good carpenters don’t blame other good carpenters for their inability to fix a broken cabinet, but that seems to be the implication of the saying that the failure to suppress the target gene “may be because [the study] has been performed by different experimenters.”
And we’ll wink at the bit about a conclusion that “cannot be supported by the scientifically correct data.” Is a conclusion supported by scientifically incorrect data, or unscientifically correct data, or even unscientifically incorrect data still a conclusion?
We guess not. Here’s the retraction notice for the paper, which has been cited 27 times, according to Thomson Scientific’s Web of Knowledge.
The following article from Journal of Neurochemistry, ‘Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury’ by Koichi Obata, Hirokazu Katsura, Kan Miyoshi, Takashi Kondo, Hiroki Yamanaka, Kimiko Kobayashi, Yi Dai, Tetsuo Fukuoka, Shizuo Akira, Koichi Noguchi, published in Volume 105, Issue 6, 2008, pages 2249–2259 (available through http://www.onlinelibrary.wiley.com), has been retracted by agreement between the authors, journal Editors in Chief, Seán Murphy and Jörg Schulz, and Blackwell Publishing Ltd. The retraction has been agreed due to a significant error with the findings reported in this paper. The quantification graphs of RT-PCR in Figs.1, 6, 10 cannot be reproduced from the existing data, and the first 2 bands in Fig.10 (Iba1 and IL-1beta) were mistakenly created from an identical band.
Sean Murphy, the journal’s editor, told us that the researchers had wanted to have the correction notice run in print, but that he and his colleagues argued otherwise:
We suggested to the authors that, instead of proceeding to print with the corrigendum, the original article should be retracted. To reach agreement took longer than it need.
As it happens, the first author, Obata, is not a stranger to correction notices. His group had one in 2009 for a 2006 paper in the Journal of Neuroscience, again involving problems with RT-PCR:
In the article “Suppression of the p75 Neurotrophin Receptor in Uninjured Sensory Neurons Reduces Neuropathic Pain after Nerve Injury” by Koichi Obata, Hirokazu Katsura, Jun Sakurai, Kimiko Kobayashi, Hiroki Yamanaka, Yi Dai, Tetsuo Fukuoka, and Koichi Noguchi, which appeared on pages 11974–11986 of the November 15, 2006 issue, there was an error in the legends for Figs. 1E, 2D, and 4, C and D. These legends described “n=4.” However, the quantification of RT-PCR and Western blots was carried out from three, not four, samples in each experiment. All statistically significant values in all figures were obtained from 3 samples. Therefore, all data were scientifically correct, only the number of samples was incorrect.
In 2007, the Journal of Clinical Investigation issued a corrigendum for one of Obata’s papers, “Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain,” again because of a problematic figure:
Yi Dai, Shenglan Wang, Makoto Tominaga, Satoshi Yamamoto, Tetsuo Fukuoka, Tomohiro Higashi, Kimiko Kobayashi, Koichi Obata,
Hiroki Yamanaka, and Koichi NoguchiOriginal citation: J. Clin. Invest. 117:1979–1987 (2007). doi:10.1172/JCI30951.
Citation for this corrigendum: J. Clin. Invest. 117:3140 (2007). doi:10.1172/JCI30951C1.During the preparation of the manuscript, the doses of ET-18-OCH3, U73122, and GF were incorrectly reported in the legend for Figure 3. The correct sentence appears below.
In some experiments, the bath solution was perfused with either a PLC inhibitor — ET-18-OCH3 (ET; 2 µM) or U73122 (2 µM) — or a PKC inhibitor, GF (0.5 µM or 10 µM) 120 seconds before SL-NH2 reapplication. The authors regret the error.
And in 2010, the JCI issued another correction for Obata’s group, this time over a 2005 paper titled “TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury,” with, you guessed it, an incorrect figure:
During the preparation of the manuscript, the number of samples used for the quantification of RT-PCR depicted in Figure 2E was stated incorrectly. The corrected legend appears below.
(E) mRNA expression of TRPA1 and TRPM8 in the DRG after inflammation, as detected by RT-PCR. Quantification of RT-PCR data is shown at right. Data represent mean ± SD; n = 3 per group. *P < 0.05 compared with the naive control.
The authors regret the error.
(Obata’s name also appears in a 2006 erratum in the Journal of Comparative Neurology that involves the misspelling of a co-author’s name.)
We noticed that Obata’s group had a paper in the Journal of Neuroscience that sounds quite similar to their retracted article. Here’s the abstract of the 2008 article,”Interleukin-18-Mediated Microglia/Astrocyte Interaction in the Spinal Cord Enhances Neuropathic Pain Processing after Nerve Injury“:
Interleukin (IL)-18 is an important regulator of innate and acquired immune responses. Here we show that both the IL-18 and IL-18 receptor (IL-18R), which are induced in spinal dorsal horn, are crucial for tactile allodynia after nerve injury. Nerve injury induced a striking increase in IL-18 and IL-18R expression in the dorsal horn, and IL-18 and IL-18R were upregulated in hyperactive microglia and astrocytes, respectively. The functional inhibition of IL-18 signaling pathways suppressed injury-induced tactile allodynia and decreased the phosphorylation of nuclear factor κB in spinal astrocytes and the induction of astroglial markers. Conversely, intrathecal injection of IL-18 induced behavioral, morphological, and biochemical changes similar to those observed after nerve injury. Our results indicate that IL-18-mediated microglia/astrocyte interactions in the spinal cord have a substantial role in the generation of tactile allodynia. Thus, blocking IL-18 signaling in glial cells might provide a fruitful strategy for treating neuropathic pain.
And the abstract from the retracted paper:
Toll-like receptors (TLRs) play an essential role in innate immune responses and in the initiation of adaptive immune responses. Microglia, the resident innate immune cells in the CNS, express TLRs. In this study, we show that TLR3 is crucial for spinal cord glial activation and tactile allodynia after peripheral nerve injury. Intrathecal administration of TLR3 antisense oligodeoxynucleotide suppressed nerve injury-induced tactile allodynia, and decreased the phosphorylation of p38 mitogen-activated protein kinase, but not extracellular signal-regulated protein kinases 1/2, in spinal glial cells. Antisense knockdown of TLR3 also attenuated the activation of spinal microglia, but not astrocytes, caused by nerve injury. Furthermore, down-regulation of TLR3 inhibited nerve injury-induced up-regulation of spinal pro-inflammatory cytokines, such as interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha. Conversely, intrathecal injection of the TLR3 agonist polyinosine-polycytidylic acid induced behavioral, morphological, and biochemical changes similar to those observed after nerve injury. Indeed, TLR3-deficient mice did not develop tactile allodynia after nerve injury or polyinosine-polycytidylic acid injection. Our results indicate that TLR3 has a substantial role in the activation of spinal glial cells and the development of tactile allodynia after nerve injury. Thus, blocking TLR3 in the spinal glial cells might provide a fruitful strategy for treating neuropathic pain.