pain

On the nature of pain

Posted on by Iasmina Hornoiu

Last week, a manatee was found in Florida waters, with the word ‘Trump’ scraped on its back. Although this kind of ruthless mutilation is horrific in itself, I started wondering if the animal felt any kind of pain.

I must admit, up until I came across the news about what happened to the manatee in Florida, I knew very little about manatees, in general. And my first thought was whether, during the scraping proccess, this manatee suffered at all. To my dismay, there were not many scientific papers dealing with the somatosensory system in manatees. However, I did find something that eased my soul a little bit: one of the articles reporting on the dreadful event states that the scratch was done in the algae growing on the animal’s back. Still, in the same article it is said that manatees have sensory hairs and nerves in their skin, which means that, if the cuts had touched the skin, they could have caused pain; not to mention the infection that the skin was at risk of, due to the open wounds.

The video below shows the above-mentioned manatee swimming, with the human-made scars on its back.

After reading all these news articles, I was left with some questions that kept occupying my mind: What are manatees?; To what extent can they feel pain?; And can we talk about ‘pain’ at all in manatees, or just nociception? Lastly, how did pain evolve throughout the animal kingdom?

What are mantees?

Also known as ‘sea cows’, manatees (Trichechus manatus latirostris) are herbivorous acquatic mammals of the Order Sirenia. As the name of their order suggests, manatees are believed to be the animals behind the myths of mermaids. For those interested in how manatees inspired mermaid legends, please check out the video below.

Manatees are the largest vegetarian animal to inhabit the sea, and they communicate with each other through high-pitched sounds. They are also very gentle and lack defense mechanisms, given that they do not have any natural enemies. However, they have become and endangered species, due to human activity, which is the manatee’s greatest threat. According to the Florida Fish and Wildlife Conservation Commission, the year 2020 was a hard one for manetees as well: 637 of them died, 90 of which were victims of boat collisions, and another 15 were killed by other interactions with humans.

Although manatees do not possess a highly acute visual system, they compensate for that by the presence of tactile hairs, or vibrissae, spread all over their body, especially on the face. This distribution of vibrissae is something unique among mammals, and to manatees it is highly useful in allowing them to navigate in the water.

Since mantees rely tremendously on tactile inputs, it comes as no surprise that their brains are organised to support somatosensation. The primary somatosensory cortex of manatees occupies 25% of their neocortex. Moreover, the sixth layer of their cortex contains clusters of neurons, known as Rindenkerne, which are believed to process information related to the manatee’s facial and bodily vibrissae. Although the Rindenkerne cells of manatees are somewhat similar to other cortical representations of vibrissae, termed ‘barrels’, in rodents, shrews, opposums and hedgehogs, Rindenkerne are unique to sirenia. These neuronal aggregates become active when manatees engage in tactile exploration and object recognition.

At the subcortical level, manatees possess three types of somatosenroy nuclei in their brainstems, namely the Birchoff’s nucleus, which receives information from flukes, the cuneate-gracile nucleus, which processes inputs from flippers and body trunk, and the trigeminal nucleus, which receives sensory inputs from facial vibrissae. Figure 1. below shows the somatosentory representations of the manatee’s body parts, in a coronal section of the brainstem. The thalamus also has specialised somatosensory nuclei, which differ in size, depending on their functional relevance to somatic sensation.

Figure 1. Left diagram based on image by Isuru Pryiaranga. Right image from Sarko et al. (2007), showing functional divisions withing the brainstem, corresponding to the manetee’s body parts. 

Given that somatosensation is so developed in manatees, one burning question is whether they feel pain.

What is pain?

Pain is different from nociception. However, pain from injury cannot occur without nociception. The latter reffers to the process of detecting injury by the activation of a special class of receptors found in the skin, as well as deep tissues and organs, known as nociceptors. The detection of potentially or actually damaging stimuli is followed by a reflex withdrawal reaction, or nociceptive behaviour, mediated by nerves in the spinal cord. The nerve fibres that detect noxious stimuli are Aδ fibres and C fibres, which have their cell bodies in the dorsal root ganglion (DRG) of the spinal cord, as shown in Figure 2.

Figure 2. Illustration taken from a student presentation at Heidelberg University, Germany.

Aδ fibres are mechano-nociceptors, meaning that they are activated by high mechanical pressures. C fibres are polymodal, which means that they respond to a variety of noxious stimulations, such as noxious chemicals (e.g., acids), extreme temperatures and high mechanical pressures. They not only encode the stimulus modality (type), but also their intensity and duration, which are relayed to reflex centres in the central nervous sytem, mediating withdrawal reactions.

The nociceptive information travels from the DRG to different parts of the brain via spinothalamic tracts (from the spinal cord to the thalamus) and sensory fibres of the trigeminal tract (from the face to the thalamus). And it is within the brain that pain happens.

Pain is a complex feeling. Many brain areas are involved in not just generating pain, but also in ameliorating it. Structures from the limbic system, such as the amygdala, receive and integrate nociceptive and affect-related information. The amygdala can lead to increased nocifensive and affective pain behavior, while, under certain circumstances, it can also contribute to endogenous pain inhibition. Pain is also processed in the hypothalamus, the basal ganglia, the insula and the somatosensory cortices. Because these areas play a role in metabolism, as well as fear, pleasure and homeostasis, the nociceptive information is integrated and modulated according to the current state of the individual. In some situations, pain becomes pathological, as it is the case in neuropathic pain, where either previously innocuous stimuli become painful (aka, allodynia), or previously painful stimuli become even more painful (aka, hyperalgesia).

There are two brainstem structures, which are highly involved in controlling pain and generating analgesia. One of them is the periaqueductal grey (PAG) and the other is the rostral ventromedial medulla. These regions exert control over pain to prioritise competing stimuli, and to maintain homeostasis and survival. You might have noticed that, in highly stressful situations you do not feel pain. This is known as stress-induced analgesia, a phenomenon whereby the brain responds to stress by the production of endogenous opioids that act as natural analgesics in the nervous system. The opioid receptors found in the brain are the same ones which analgesic drugs, such as synthetic opioids and morphine, act on to relieve pain.

The evolution of pain

Many animal taxa have nociceptors. A schematic of the evolutionary development of nociceptors and the types of noxious stimuli they respond to is presented in Figure 3. In order to process nociceptive inputs, animals need a central nervous system (spinal cord and brain). It might come as a surprise that such a system, though at different levels of complexity, is found in all kinds of animals, including insects (like Drosophila melanogaster, the fruit fly), C. elegans (a type of worm highly studied in neurosciences), fish, amphibians, reptiles, birds and, of course, mammals.

Figure 3. The different types of nociceptors across animal taxa, from an evolutionary perspective.
Taken from Sneddon (2017)

Life-history shapes pain perception. A very interesting example is the African naked mole rat, which lives in underground burrows that are poorly ventilated, hence contain high carbon dioxide levels. As a result, the C fibres of the naked mole rat are unresponsive to acid, which means that, while other mammals find acidic environments nociceptive, the African naked mole rat does not.

When it comes to acquatic animals, such as manatees, they are expected to have differences in their sensory system compared to terrestrial ones, due to distinct ecological and evolutionary pressures. In water, any chemicals become dilluted, shifts in temperatures are less common, and there is no mechanical damage due to falling. Thus, acquatic animals are possibly at a lower risk of damage than terrestrial animals, which has implications on their nociceptive system.

As far as manatees go, it is still unclear to what extent they feel pain. The fact that they are an endangered species makes is difficult to study them. But given that they posses a very well-developed somatosensory system, which is even more advanced than in other mammals, it is expected that manatees are familiar with pain. Moreover, we still do not know enough about their stress, fear, memory and pleasure systems, which all play a role in pain processing.

It would be great if we managed to achieve a better understanding of these amazing marine animals. But, until then, let us enjoy their existance peacefully, without interfering violently with their lifestyles and without exposing them to any potential pains.

For a more in-depth view on pain, as well as more information about manatees, I highly encourage you to read the papers and articles listed in References.

Special thanks to Isuru Priyaranga for creating the cover image. He is a fellow blogger and YouTuber, and I highly recommend visiting his blog and YouTube Channel.

References

Fear and the amygdala

Posted on by Iasmina Hornoiu

What is fear? Why are we sometimes afraid? Can fear be inhibited? What produces fear – the brain or the heart?

It is definitely the brain! More exactly, something in the brain – a tiny, almond-shaped structure, which sits anteriorly to the hippocampus, called the amygdala. This small part of our brain is to blame for  the perception of fearful stimuli and the physiological responses (increased heart rate, electrodermal responses etc.) to fearful stimuli.

As part of the FEAR system, the amygdala connects to the medial hypothalamus and the dorsal periaqueductal grey matter (in the midbrain), which is important in pain modulation in the dorsal horn of the spinal cord, as well as to sensory and association cortices. The lateral nucleus of the amygdala receives inputs from different brain regions, thus allowing the formation of associations, required for aversive conditioning. Following the processing in the lateral nucleus, information about the stimulus is, then, projected to the central nucleus of the amygdala, where an appropriate response to the stimuli is initiated, provided that the stimuli are detected as threatening or potentially dangerous.

The amygdala is involved in emotional learning and memory, modulating implicit learning, explicit memory, attention, social responses, emotion inhibition and vigilance.

You can find the article on memory here, to brush up a bit.

  • Implicit memory is a type of learning, which cannot be voluntarily reported or remembered. It includes the memories for skills and habits, for procedural knowledge, grammar and languages, priming, simple forms of associative learning and classical conditioning. The latter is particularly important for fear. It involved a conditioned stimulus (CS) and an unconditioned, painful/fearful stimulus (US), with US preceding CS and determining a fearful response to CS. This type of fear learning is adaptive and is known as sensitisation or acquisition.

There are two different pathways in the amygdala, important for fear conditioning. The “low road” pathway: sensory information projects to the thalamus, which directly communicates with the amygdala; this pathway is fast, modulating rapid responses of the amygdala to different types of fearful stimuli. The “high road” pathway is an indirect pathway: sensory information projects to the thalamus and from there, it is conveyed to the sensory cortex for a finer analysis; the sensory cortex, then, communicates the processed information to the amygdala. This pathway ensures that the sensory stimulus is the conditioned stimulus. So the responses of amygdala to threatening stimuli are both rapid and sure.

  • Explicit memory refers to the memory of facts and events; in the case of fear is means the processing and retention for a long time, of emotional events and information. For this type of fear learning, the amygdala interacts with the hippocampus. There is a distinction between the formation of memory for aversive experience (fear conditioning), which is based on previous experience, and explicit learning (in the hippocampus), which involves learning and remembering aversive properties of different threatening stimuli. The memory in the hippocampus is enhanced by arousal produced in the amygdala. The activation of the amygdala can make different cortical areas, not just the hippocampus, more receptive to stimuli that are adaptively important, thus ensuring that unattended, but important stimuli gain access to consciousness.
  • Social responses involve the ability to recognise a stimulus as good, bad, neutral or arousing. This ability, however, does not depend on the amygdala. There is one exception here, otherwise we wouldn’t be talking about it in the context of fear mediated by amygdala – fearful facial expressions. According to Darwin, social species, like humans, use facial expressions to detect internal emotional states of other members of the group. This function, mediated by the amygdala, is crucial in the emotional regulation of human social behaviour. Damage to amygdala has been demonstrated to result in impairment of the patient to identify fearful faces correctly and, therefore, react to them, accordingly. It should also be noted there is no need for the subject’s awareness of the fearful stimulus, for the amygdala to respond. In other words, when a fearful facial expression is presented subliminally, the amygdala will still show activation.
  • Inhibition of fear – it is actually very difficult to escape your own fears, as fear proves to be resistant to voluntary control. However, there is a process called extinction, a method of classical conditioning, where a CS previously associated with an aversive US in presented alone for a number of times, until the CS no longer signals the fearful stimulus. If the US is presented again, after the passage of time, it will evoke fear responses, but in different brain areas. So, the learned fear has been retained in memory, but extinction learning eliminates the response to fear. This mechanism of extinction relies on the activity of NMDA glutamate (excitatory) receptors in the amygdala. When these receptors are blocked, extinction is inhibited (so you will react to fearful stimuli) and when they are active, extinction is augmented (you no longer respond to aversive stimuli).
  • Vigilance – the amygdala is not necessary for the conscious experience of emotional states, but it plays a major role in increasing the vigilance of cortical response systems to emotional stimuli.

Memories about fearful events, just like other types of long-term memory, become permanent through a process of gene expression and novel protein synthesis, which is known as consolidation. Upon retrieval, the memories become susceptible to change and alteration, before they are reconsolidated, which involves additional protein synthesis.

The fact that humans (and probably other animals as well, I am sure, although not widely proven) have the ability to distinguish between emotional information and unemotional information is regarded as an evolutionary advantage. Emotional stimuli signal dangers and the ability to detect and appropriately react to them increases the chance of survival. However, exacerbated fear is detrimental to the individual who experiences it and is a sign of pathology. For instance, in atypical monopolar depression, which includes anxiety as one of the main symptoms, the amygdala is overactive and it determined lowering the threshold for emotional activation and abnormal reactions to stressful stimuli. A similar pattern can be seen as a result of partial chronic sleep deprivation or complete acute sleep deprivation.

References

 Beatty, 2001. The Human Brain – Essentials of Behavioural Neuroscience, Sage Publications Ltd., pg. 293-296

Bernard et al., 2007. Cognition, Brain and Consciousness – Introduction to Cognitive Neuroscience. 1st edition. Elsevier Ltd., pg. 373-383

Gazzaniga et al., 2002. Cognitive Neuroscience – The Biology of Mind. 2nd edition. W.W Norton & Company, Inc., pg. 553-572

Image by  Saya Lohovska. You can find her arts page here.