Posts Tagged Pain

Needle Free Vaccination

How good would this be? According to a recent TED talk by Mark Kendall it could soon become reality (http://www.ted.com/talks/mark_kendall_demo_a_needle_free_vaccine_patch_that_s_safer_and_way_cheaper.html).

Instead of using a needle and syringe the vaccine is applied via a patch that is placed on the skin. The patch contains thousands of projections that release the vaccine into the top layers of the skin. As well as being pain free the administration of the vaccine into the skin, rather than the muscle, also generates a more powerful immune response. This means that much less vaccine is required (up to one hundredth of the traditional dose) lowering the cost and decreasing the possibility of undesirable side effects.

The vaccine that coats the patch is in a dry form. Therefore, it does not need to be refrigerated, unlike traditional vaccines, and will retain its potency at 23 C for up to a year. This makes it much more feasible to use in countries where electricity and refrigeration are difficult to guarantee, such as Papua New Guinea which has only 800 refrigerators. Patch trials are due to start there soon.

Dr. F. Bunny

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Marathon Man

“But why, some say, the moon? Why choose this as our goal? And they may well ask why climb the highest mountain? Why, 35 years ago, fly the Atlantic?”

“We choose to go to the moon in this decade and do the other things, not because they are easy, but because they are hard.” John F. Kennedy (http://er.jsc.nasa.gov/seh/ricetalk.htm)

So too my son and I chose to run the Melbourne Marathon last Sunday, not because it was easy, but because it was hard. Little did I realise exactly how hard it was going to be. I have been running for five years, gradually building up my distance and endurance. When I completed the half marathon in July in good time with relatively few aches and pains I felt ready to embark on the real thing. Little did I realise that a marathon is so much more than twice a half marathon. My previous longest run was 24 km and that lack of 30+ km experience came back to bite me on the day.

I completed the first half of the marathon with relative ease because my body was used to the pounding it received over that distance. But after about 25 km the legs began wondering what was happening and why we had not gone to collect our drink and finisher’s medal.

I ran on, inspired by a particularly energetic Motörhead track blasting into my ears. I began to set myself small goals to avoid thinking about how far I still had to run. A little cheer erupted in my head when I hit the 30 km mark. After 32 km I knew that the remaining kilometres could now be measured in single digits. Unfortunately the knowledge didn’t stop me flagging to the extent that, around 34 km, a fellow runner felt compelled to give me an encouraging pat on the back as she glided past. Still, I was doing better than that poor fellow lying on the stretcher, surrounded by paramedics, with a drip in his arm.

At 35 km there were only seven kilometres to go. Seven kilometres! I often ran seven kilometres. I could easily manage seven kilometres. Are you joking? There are still seven kilometres to go! And then the heavens opened up but I was in too much pain to notice. I kept slowing to a walk, willing myself back into a run and then, when the knee pain got too much, dropping back to a walk. At 37 km the inspirational speech given at the start of Tough Mudder (http://www.youtube.com/watch?v=kUwXTfWxCTM) burst into my ears. I “hoorahed” myself back into a run.

Turning the corner at 40 km, two kilometres from home, it felt like someone stuck a knife into my right knee. I crumpled but didn’t go over, dimly aware that an official photographer was busy recording every grimace to sell to me later. I slowed to a walk, a stumble, a shuffle. I figured I could manage the last two kilometres even if I had to crawl over the line, but that was not how I wanted to go out. I kept trying different running techniques to ease the pain in the knee: turning the leg outwards or shuffling sideways. I even contemplated running backwards. All around other runners ran past me.

I felt despondent, and then I saw the light towers of the MCG, the world’s greatest sporting stadium, the magnificent home of Australian Rules Football. The final 400 metres involved running a lap on the hallowed turf. No way was I going to walk this. I gritted my teeth and propelled myself into a lopsided, stumbling jog. I ran into the stadium, the stands of that great arena surrounding me. At 200 metres I stumbled and almost fell, but had just enough energy left to pass one final runner before collapsing over the finish line into the arms of my waiting son (I encouraged him to go on ahead at 25 km when it became obvious that I could no longer keep up). Sobbing and laughing simultaneously I felt so incredibly proud of us both.

As the adrenalin finally left my body I was utterly and totally spent. I had given my all, could barely move and felt close to passing out. A banana and a Powerade managed to restore some semblance of normality.

Now, three days later, I still feel tremendously buoyed by our accomplishment. I am sure family and friends are well and truly sick of hearing about it, which is why I thought I would tell you.

No doubt there are many who would consider this to be a ridiculously foolhardy expenditure of energy. Why run 42.2 km when you can drive that distance in a fraction of the time with absolutely no pain involved? I think this is one of the things that define us as a species. Had we taken the easy way and not risen to the challenge, made the effort or sacrificed our comfort I suspect we would all still be living in caves finger painting on the walls.

And now, I am going to have a nice lie down.

Dr. F. Bunny

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Wake Me When It Hurts

Now that we know all vertebrates and probably the majority of invertebrates feel pain what about young animals? Until an animal (or human) reaches a certain stage of development its brain is presumably not sufficiently mature enough to recognise and register that a painful event is occurring. This does not mean painful events do not occur or that the body does not respond to them in some way. It just means that the brain is not able to consciously register the event. This happens during surgery when an animal (or human) is anaesthetised. The surgical event is still painful but the part of the brain that recognises and responds to this fact has been switched off by virtue of the anaesthetic. Extrapolating from this a foetus is effectively unconscious and unaware of painful stimuli until its brain has become complex enough to develop consciousness.

The electrical activity in the brain can be measured via an electroencephalogram (EEG). Very early on in development the EEG is absent i.e. there is no detectable brain activity. As the animal develops EEG activity begins to appear. The time when this occurs relative to an animal’s birth depends on how mature it is after it is born. Lambs are born fairly well developed and are able to stand and walk shortly after birth. They develop EEG readings and therefore conscious perception after about 80% of the pregnancy has elapsed (similar to humans) and are born more or less fully conscious, although their EEG shows significant continued maturation during the first week of life. Lamb EEG responses to castration are not as great at one to two days after birth as they after one week post birth.

Rats are reasonably immature when born and have no detectable EEG. EEG signals don’t appear until 12 to 18 days after birth. Rats whose tails are clamped five to seven days after birth do not respond, while those clamped after 12 days do.

Marsupials are an interesting case because they are born at a very immature stage and crawl into their mother’s pouch where they complete most of their development. Interestingly they are able to complete that task even though their brain consists of only two layers of cells. In the tammar wallaby EEG activity does not appear until after 120 days of pouch life (total pouch time is approximately 250 days). Earlier than this and there is no response to toe clamping (Diesch et al 2007).

The main assumption here is that EEG activity correlates with consciousness. While this seems valid it is impossible to be certain and, even if the young animal does not consciously experience pain, the body can still react to painful stimuli by releasing stress hormones, withdrawal reflexes and changes in brain blood flow. There is some suggestion that while the animal cannot consciously perceive the pain it becomes sensitised to it such that it develops an increased perception of pain after birth that could become permanent (http://www.daff.gov.au/__data/assets/pdf_file/0019/1046431/25-craig-johnson.pdf). As always it seems prudent to err on the side of caution and avoid causing pain wherever possible.

Dr. F. Bunny

Reference

Diesch, T.J., D.J. Mellor, C.B. Johnson, and R.G. Lentle. 2007. Responsiveness to painful stimuli in anaesthetised newborn and young animals of varying neurological maturity (wallaby joeys, rat pups and lambs). Proceedings of the 6th World Congress on Alternatives and Animal Use in the Life Sciences, Tokyo. Pp. 549-552.

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Happy As A Clam

Exactly how happy are clams? Not very, according to Mark Miller of the Huffington Post (http://www.huffingtonpost.com/mark-c-miller/happy-as-a-clam_b_901054.html), who cites Dr. Patra Gupta of the Kerala Institute of Undersea Study. Dr. Gupta states that “the clams’ liquid secretions are identical in DNA structure to human tears. Clams also have less mobility than almost any other living creature, one of the sure signs of depression. They don’t fight back, don’t react to pain, take no interest in their appearance, don’t play or communicate. I’ve seen suicidal individuals with more zest for life, coma patients with a greater level of activity. These clams have less than zero interest in living; we might as well eat them.”

Gupta’s team attempted to generate some degree of happiness or life in the clams, introducing them to the far peppier shrimp, scallops, crab, lobster, even angel fish. But nothing. “Those clams couldn’t have cared less; they scarcely peered out of their shells. It was quite rude, actually. We’re getting in touch with a fish therapist to see if counselling might help, but quite honestly, I’m not holding out a lot of hope for it. I think we’re just going to have to face the fact that clams as a species are severely depressed.”

Maybe they were depressed because they were examined at low tide because the complete expression is, “happy as a clam at high water” (http://www.phrases.org.uk/meanings/as-happy-as-a-clam.html). High tide is when clams are much less likely to be predated, a good reason for happiness. Apparently the phrase originated from the US in the early nineteenth century.

The idea of happiness implies some kind of functioning nervous system, which makes me wonder, not about the clam’s state of mind but, carrying on from the previous post, can clams feel pain? Lobsters and crabs do have what can be termed a brain and, despite what our lobster eating friends would have us believe, do appear to feel pain and don’t appreciate being boiled. In a 2008 study a noxious stimulus was applied to the antenna of prawns. The prawns immediately began grooming the treated antenna and rubbed it against the side of the tank. This activity did not occur if the prawns were treated with benzocaine, a local anaesthetic (Barr et al 2008). In a much earlier study lobsters tossed into boiling water took up to seven minutes to die, all the time writhing, thrashing and convulsing (Baker 1975) (http://www.shellfishnetwork.org.uk/facts/fact4.htm).

While this appears extremely disturbing it is important to determine if these movements are the result of an organism in pain or merely a reflex to a noxious stimulus without a conscious perception of pain. While this may seem counter intuitive the brain of so called lower life forms is not as all important as it is for higher life forms. Many tasks are delegated to the spinal cord or other clusters of neurones. This can even be seen in higher vertebrates. Many years ago, while necropsying a freshly dead horse, I cut through a nerve in the groin region and promptly received an impressive kick for my trouble. The horse was well and truly dead, could feel no pain and yet reacted to the stimulus. A similar event occurred during a lizard necropsy. The lizard had a severed spine and, at the conclusion of the procedure, I was left with the lizard’s tail, back legs and pelvis. When I pinched a toe the leg and tail both wriggled, even though they were no longer attached to the top half of the body. (As a digression freshly dead reptiles often still have beating hearts when they are opened up. They are, however, definitely dead. If the heart is removed from the body it will continue to beat, lying on the table by itself, for up to an hour. It certainly creeps the students out and can make it somewhat tricky to confirm death in a reptile.)

It can be difficult to differentiate reflex from pain response in a live animal of limited reactions. I feel that, if the animal responds to pain killers by not reacting to the noxious stimulus, like the prawns and the fish in the previous post, then it is probably experiencing pain. The implication here is that the animal has pain receptors that can be chemically blocked. Pain and opioid receptors have been identified in snails, nematodes, crustaceans and insects (http://en.wikipedia.org/wiki/Pain_in_invertebrates).

But the clincher, for me at least, is the phenomenon of avoidance learning. To demonstrate this effect a light was shone on a crayfish. Ten seconds later the crayfish received an electrical shock. The crayfish learned that the light was associated with the shock and rapidly moved away when the light came on, thus avoiding the shock. A similar phenomenon was reported for Drosophila flies. In this case the electrical shock was paired with an odour. The flies quickly learned to fly away from the odour whenever they detected it (Elwood 2011). This cannot just be reflex. These animals are displaying a learned response and acting peremptorily to avoid a painful stimulus.

Which brings us back to clams. As far as I can tell clams do not have a brain as such but do have clusters of nerve cells called ganglia, which allow them to respond to certain stimuli. Pain receptors have been identified in their snail relatives and presumably exist in clams. Given that the avoidance of pain is universally beneficial to all forms of animal life and most clams are capable of movement, at least some of the time, I am prepared to give them the benefit of the doubt and say that they can feel pain. I hope that, at least, makes them happy.

Dr. F. Bunny

References

Baker, J.R. 1975. Experiments on the humane killing of lobsters (Homarus vulgaris) and crabs (Cancer pagarus). Part 1. The killing of lobsters by gradual heating. Scientific papers of the Humane Education Centre 1: 1-10.

Barr, S., P.R. Laming, J.T.A. Dick and R.W. Elwood. 2008. Nociception or pain in a decapod crustacean? Animal Behaviour 75: 745-751.

Elwood, R.W. 2011. Pain and suffering in invertebrates? Institute for Laboratory Animal Research 52: 175-184.

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Something Fishy Going On Around Here

I have quite a spectacular goldfish swimming around its tank. His (or her) name is Witchhaven. That is what happens when you let your kids name the animals. I won’t even mention Cork and Spider-man, two former chickens. Anyway Witchhaven is the last of his kind. A decision was made that when all the fish died we would move from cold water fish to tropical ones. Witchhaven continues to stubbornly cling to life long after his contemporaries have moved on.

Interestingly, while we have decided to allow Witchhaven to live out the term of his natural life, I would be perfectly within my rights to shove a sharp barbed hook into his mouth and lift him out of the water with his full body weight hanging by his lip from the hook. This is called fishing. While fish do get a mention in the 1986 Prevention of Cruelty to Animals Act the act does not apply to any fishing activities authorised by and conducted in accordance with the Fisheries Act 1995 (http://www.austlii.edu.au/cgi-bin/sinodisp/au/legis/vic/consol_act/poctaa1986360/s6.html?stem=0&synonyms=0&query=fishing). Hooks are, of course, regarded as an integral part of recreational fishing and, as the act clearly states, “recreational fishing equipment means any fishing equipment prescribed in the regulations to be recreational fishing equipment.” I love bureaucracy.

Intriguingly were I to pull my cat along by a hook embedded in its lip I would get into trouble as this, no doubt, falls under the definition of someone who “wounds, mutilates, tortures, overrides, overdrives, overworks, abuses, beats, worries, torments or terrifies an animal (http://www.austlii.edu.au/cgi-bin/sinodisp/au/legis/vic/consol_act/poctaa1986360/s9.html?stem=0&synonyms=0&query=cruelty).” Unfortunately it is perfectly fine to do that to our aquatic friends, because that is in the interests of sport, which override all other considerations.

And don’t think you can get out of it by saying fish don’t feel pain. They have a brain and a nervous system and the avoidance of noxious stimuli has the same benefit for them as it does for us. There is certainly no shortage of studies supporting the notion that fish feel pain.

A 2003 study was conducted where a noxious chemical was rubbed onto the lips of rainbow trout and their behaviour compared with untreated fish. The treated fish rocked from side to side and rubbed their lips into the gravel and on the sides of the tank. Their breathing rate also increased. When these fish were treated with morphine, a potent pain killer, these abnormal activities decreased, indicating analgesia (Sneddon 2003).

A similar 2007 study found morphine blocked the effects of a noxious stimulus (acetic acid) that had been injected into the cheeks of flounder (Newby et al 2007).

Koi carp showed a marked decrease in interactive behaviour, food consumption and activity following surgery. This did not occur if the carp were given butorphanol (another pain killer) or morphine (Baker et al 2010).

I could go on but it is pretty obvious that in this day and age the only people who still argue against fish feeling pain are those with a vested interest in perpetuating those painful activities i.e. anglers.

So go forth and fish, if you must, but don’t delude yourself that the marlin on the end of your hook, leaping so magnificently out of the water, is doing it for fun.

Dr. F. Bunny

References

Baker, T.R., B. Cummings, S.M. Johnson, and K.K. Sladky. 2010. Comparative analgesic efficacy of morphine and butorphanol in koi (Cyprinus carpio) undergoing gonadectomy. Proceedings of the AAZV AAWV Joint Conference. Pp. 203-204.

Newby, N.C., A.K. Gamperl, and E.D. Stevens. 2007. Cardiorespiratory effects and efficacy of morphine sulphate in winter flounder (Pseudopleuronectes americanus). American Journal of Veterinary Research 68: 592-597.

Sneddon, L.U. 2003. The evidence for pain in fish: the use of morphine as an analgesic. Applied Animal Behaviour Science 83: 153-162.

 

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