Insights into pain perception

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ANIMAL ANGST: Fish, and the worms used as bait in fishing, feel pain. - Photo: AP
ANIMAL ANGST: Fish, and the worms used as bait in fishing, feel pain. - Photo: AP

Plants cannot feel pain as the key enzyme for producing it is absent

LAST YEAR, a heated debate raged in England about whether fish feel pain or not. Soon enough, it was joined by the scientists. Opinion was divided roughly fifty-fifty. One group said they do, while the opposite camp said no, fish do not feel pain. Fishing enthusiasts, naturally, joined the latter group. Reading about the issue, I began wondering what this sensation called pain is and what the biochemical and physiological requirements are for an individual organism to feel it.

Cellular pathway

Some recent papers by Dr. Ashok Kulkarni and his associates, at the US National Institutes of Health, clarify some of the features that go to signal the sensation in mice. Their paper in the January 17, 2006 issue of the Proceedings of the National Academy of Sciences, suggests a cellular biochemical pathway that tells us how mice experience pain. Since essentially the same biochemical pathways operate in many organisms, the results of this paper help us understand what pain is, how it is felt - and perhaps even which organisms are capable of experiencing pain and which are not.Let me qualify right away that in talking about pain, I am not referring to the kind that poets pen about denied love, or of Shakespeare's `parting is a sweet sorrow.'Scientists distinguish between this, which they call affective or emotional, and sensory or discriminative which is felt when a pin pricks. The sensory component of pain is also called nociception - the prefix `noci' from the Latin for injury or trauma and `ception' for perception. Nociception is required for survival and the maintenance of the integrity of the organism. Of course one should not have it become chronic or long lasting, since then it leads to anxiety and related symptoms, affecting the psychological well- being. What cellular events are involved in nociception has been a subject of interest and activity. We now know that there are specific types of cells and molecules that regulate nociceptive activity. The basic aim of much of such studies has been to understand the molecular mechanisms that signal pain. With the advent of DNA technology, it has been possible to study the genes involved in nociception. This has usually involved taking a freak animal which feels no pain and a `normal' one, and identifying which genes are active in one compared with the other. Indeed there are special laboratories and animal houses that collect and store such freak animals, and provide them to scientists for research. Some of these animals are born with one or more genes mutated or missing and display specific deficiencies, enabling researchers to identify the function of the genes.

Studying the function

It is now also possible to genetically modify animals - either introduce a chosen gene, or `knock out' genes - and grow generations of them. This technology allows us to study the function of chosen genes in the live animal. Dr. Kulkarni is an expert in generating such transgenic mice and studying their physiology.Experiments using such genetically modified mice had allowed earlier workers to identify several genes involved in pain perception, and also the proteins that these genes produce in the cells. One of the key proteins implicated in the process is the enzyme called cyclin dependent kinase 5 or Cdk5. This protein is in turn activated by two others, called p35 and p39. Kulkarni and associates have now provided the molecular role of Cdk5 in signalling the sensation of pain. In order to do so, they first generated in the laboratory mice in which the gene for the activator p35 is `knocked out', and also mice in which this gene is `overactive'. Comparison of the pain felt by the p35 knockouts, p35 over-expressers and normal mice allowed them to tease out the molecular features responsible for nociception. The knockouts displayed significantly lower activity of the enzyme Cdk5 in response to painful thermal stimuli. (Radiant heat from a projector lamp was aimed at the paw of a mouse, and the speed with which it withdrew the paw was measured as the response).The overexpressing mice were hypersensitive to pain, and Cdk5 activity here was measurably higher than that of normal mice. These results suggest that Cdk5/p35 dependent factors are involved in pain signalling. Now that we have a clue to the role of the enzyme Cdk5 in mice, we can ask whether other organisms share this mechanism and feel pain likewise. Cdk5 and related enzymes are vital players in the process of division of cells and their subsequent assembling to make tissues, organs and limbs. The role of these Cdk enzymes, the molecules that control them and the genes that code for them were elucidated by Drs. Leland Hartwell, Timothy Hunt and Paul Nurse, who were awarded the Nobel Prize for Medicine in 2001. We now know that the cyclical process of growth and division of cells is common to organisms, and the Cdk family too is ubiquitous.

Comfort for vegetarians

Two years ago Drs. Z. Guo and J. Stiller of East Carolina University analysed the presence of Cdk family members in animals, yeasts, plants and protists. Looking specifically at Cdk5, they pointed out that none of these Cdks in plants associates strongly with the Cdk5 group. Given this, and the knowledge that Cdk5 is important for the proper development of the nervous system, we may comfort vegetarians by stating that plants cannot feel pain. They neither have Cdk5 nor the nervous system. Fish? They do have Cdk5 and p35 and thus would feel pain. What about the worm used as bait in fishing? They do too, Dr. Kulkarni tells me, since they have cdk5. What about yeasts, which too have Cdk5? Years ago in a spoof aimed at animal activists, a colleague asked whether we are not terrorising and traumatizing yeast when baking bread. If Cdk5 and p35 are the route to pain, may be hypersensitive (not sensory but affective) vegetarians are better off sticking to chapatti and rice, rather than bread!D. BALASUBRAMANIAN



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