The death of John Stuart Mill

This article surveys the fiercely contested posthumous assessments of John Stuart Mill in the newspaper and periodical press, in the months following his death in May 1873, and elicits the broader intellectual context. Judgements made in the immediate wake of Mill's death influence biographers and historians to this day and provide an illuminating aperture into the politics and shifting ideological forces of the period. The article considers how Mill's failure to control his posthumous reputation demonstrates both the inextricable intertwining of politics and character in the 1870s, and the difficulties his allies faced. In particular, it shows the sharp division between Mill's middle and working class admirers; the use of James Mill's name as a rebuke to his son; the redefinition of Malthusianism in the 1870s; and how publication of Mill's Autobiography damaged his reputation. Finally, the article considers the relative absence of both theological and Darwinian critiques of Mill.

HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain

Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug-induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40% to 50% as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.