Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury. Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived (...) from lipopolysaccharide. Additionally, -naltrexone, -naloxone, and -naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by -naloxone and -naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists -naloxone and -naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with -naloxone is of potential clinical relevance. This is because -naloxone is an antagonist that is inactive at the -opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that -opioid antagonists such as -naloxone may be useful clinically to suppress glial activation, yet -opioid agonists suppress pain. (shrink)

Peckham claims that my "behavior" in dealing with the quotations in Natural Supernaturalism is the same, in methodology and validity, as the interpretative behavior of Booth's waiter. But the great bulk of the utterances in my quotations—and no less, of the utterances constituting Peckham's own essay—do not consist of orders, requests, or commands. Instead, they consist of assertions, descriptions, judgments, exclamations, approbations, condemnations, and many other kinds of speech-acts, the meanings of which are not related to my interpretative behavior, even (...) in the indirect way in which the meaning of Booth's order is related to the future behavior of his waiter. M. H. Abrams, author of Natural Supernaturalism and The Mirror and the Lamp and Class of 1916 Professor of English at Cornell University, responds in this essay to Morse Peckham's "The Infinitude of Pluralism" . Morse Peckham, in his Critical Response, was commenting on issues raised by the forum on "The Limits of Pluralism" , to which M. H. Abrams contributed. Previous contributions to Critical Inquiry are "Rationality and Imagination in Cultural History: A Reply to Wayne Booth" and "The Deconstructive Angel". (shrink)

In retrospect, I think I was right to compose Natural Supernaturalism by relying on taste, tact, and intuition rather than on a controlling method. A book of this kind, which deals with the history of human intellection, feeling, and imagination, employs special vocabularies, procedures, and modes of demonstration which, over many centuries of development, have shown their profitability when applied to matters of this sort. I agree with Booth that these procedures, when valid, are in a broad sense rational, and (...) subject to analysis and some degree of definition. But the rules underlying such a discourse are complex, elusive, unsystematic, and subject to innovative modification; they manifest themselves in the intuitive expertise of the historian; and the specification of these rules should not precede, but follow practice. . . . After the fact, nevertheless, a book like Natural Supernaturalism is subject to close critical inquiry about its methods and rationale. I am grateful to Booth for opening up such an inquiry, and for doing so in a way that is not only disarming, but seems to me to be the most promising of useful results. That is, instead of adopting a prosecutorial stance, demanding: "Justify the rationality and probative force of what you have done; it looks dammed suspicious to me," he has adopted the friendly tactic of saying: "Your book, in my experience of it, has yielded discoveries that I want to call knowledge, by methods, however deviant from standard rubrics of valid reasoning, that it seems irrational to call non-rational. Let's set out to clarify what these methods are, and to see what grounds we can find for the claim that they provide warranted knowledge." M.H. Abrams' contributions to Critical Inquiry are "The Deconstructive Angel" and "Behaviorism and Deconstruction: A Comment on Morse Peckham's 'The Infinitude of Pluralism'". (shrink)

We consider conditionals of the form A ⇒ B where A depends on the future and B on the present and past. We examine models for such conditional arising in Talmudic legal cases. We call such conditionals contrary to time conditionals.Three main aspects will be investigated: Inverse causality from future to past, where a future condition can influence a legal event in the past (this is a man made causality).Comparison with similar features in modern law.New types of temporal logics arising (...) from modelling the Talmudic examples. We shall see that we need a new temporal logic,which we call Talmudic temporal logic with linear open advancing future and parallel changing past, based on two parameters for time. (shrink)

In this paper, the authors have detected a new effect in the area of geomagnetism, related to the behavior of a magnetic dipole freely floating on water surface. An experiment is described in the present paper in which a magnetic dipole fixed upon a float placed on non- magnetized water surface undergoes displacement along with reorientation caused by fine structure of the earth's magnetic field. This fact can probably be explained by secular decrease of the earth's major dipole moment. Further, (...) a detailed study of the phenomenon may create interesting premises for its practical use, particularly for the analysis of fine structure of geomagnetic field and its time-dependent anomalies. A strange behavior of some sea fish species prior to strong earthquakes may be explained if the fish are assumed as 'live magnetic dipoles'. (shrink)

Disagreement is a pervasive feature of human discourse and a crucial force in shaping our social reality. From mundane squabbles about matters of taste to high-stakes disputes about law and public policy, the way we express and navigate disagreement plays a central role in both our personal and political lives. Legal discourse, in particular, is rife with disagreement - it is the very bread and butter of courtroom argument and legal scholarship alike. Consider a debate between two legal philosophers, Ronald (...) and Herbert, about the Eighth Amendment of the U.S. Constitution, which prohibits ‘cruel and unusual punishment’. Ronald asserts: ‘It is the law that capital punishment is prohibited’. In response, Herbert states: ‘It is not the law that capital punishment is prohibited’. We intuitively think Ronald and Herbert are disagreeing, which reveals in the fact that they are licensed to use ex¬pressions like no (it isn’t) and nuh-uh when responding to their opponent’s claim. But despite the ubiquity and significance of legal disagreement, its precise nature remains elusive. This chapter discusses what exactly is going on when two people disagree about what the law requires, and how can hybrid theory may answer this question. (shrink)

The work of many scholars in the last hundred years has helped us to understand the nature and origins of the treatise which we know for short as the Contest of Homer and Hesiod. The present state of knowledge may be summed up as follows. The work in its extant form dates from the Antonine period, but much of it was taken over bodily from an earlier source, thought to be the Movaelov of Alcidamas. Some of the verses exchanged in (...) the contest were current even earlier, and some scholars have supposed that the story of a contest went back to the fifth, sixth, or even eighth century; but this is now much doubted. (shrink)

The sensorimotor theory promises a fresh explanation of phenomenal consciousness, for instance of the feeling of experiencing redness. But can it also be extended to explaining aspects of phenomenal consciousness which are only possible thanks to culture, thanks to our embeddedness in social practices? In this paper, I argue that the sensorimotor theory is in need of such an extension, and I make a proposal for how this might be accomplished. I concentrate on one example of culturally shaped experiences, namely (...) on feeling socially shaped emotions, and in particular moral emotions, such as resentment, guilt, forgiving someone, etc.. My main suggestion is this: in our case of enculturated humans, our implicit knowledge of sensorimotor contingencies is informed by, and transformed by, sociocultural practices. There are, I suggest, 'sociocultural contingencies', the mastery of which can contribute to one's phenomenal consciousness. For example, in order to have the experience of feeling resentment or guilt, one has to engage in an actual fight and make use of one's sociocultural skills of blaming someone or of justifying oneself. (shrink)

Several of the treatises and lectures that make up the Hippocratic corpus begin with more or less extended statements about the physical composition and operation of the world at large, and approach the study of human physiology from this angle. We see this, for example, in De Natwra Hominis, De Flatibus, De Carnibus, De Victu; it was the approach of Alcmaeon of Croton, Diogenes of Apollonia, and according to Plato of Hippocrates himself. The work known as De Hebdomadibus would appear (...) to be a prime example of the type. The first twelve chapters are cosmological. They are dominated by two ideas: that everything in nature is arranged in groups of seven, and that the human body is constructed on the same pattern as the whole world. In the later part of the book we pass to the subject of fevers, their causation and treatment. But as Roscher observed, the cosmology and the pathology do not belong together. (shrink)

The law and society occasionally impute consent to an agent despite a clear lack of actual consent. A common type of such ‘fictitious consent’ is constructive consent. In this practice, we treat an agent as if she consented to Φ because she did Ψ. By examining how constructive consent operates in law and daily life, I show that our treatment of agents in these cases bears no normatively relevant resemblance to consent because it is grounded in values and concerns other (...) than autonomy. Thus, the practice may diminish the very autonomy consent proper seeks to promote. Hiding this potential for conflict creates the risk moral concerns will not be appropriately balanced when deciding on the permissibility of an action. We thus ought to be explicit that such cases don’t involve consent and its common justification. (shrink)

(No abstract is available for this citation).