Painful touch

Defining pain is not as straightforward as many might assume. Intuitively, it seems reasonable to define pain as the response to tissue damage or disease. Simply put, it hurts when we hit our hand with a hammer and it hurts because we cause damage to the hand. Unfortunately that definition is problematic for at least two reasons. First, it tends towards tautology and circularity because it reduces to the statement that pain is caused by painful stimuli. In other words, pain is caused by pain. Second, it encourages a focus on a stimulus, which does not feel pain, rather than on a person, who does feel pain. Pain cannot be defined by stimuli, pain must be defined by the content of painful experience. Most pain researchers adopt a definition of pain that emphasises the sensory, cognitive and affective content of pain experience that typically follows a noxious stimulus. This understanding of pain is supported by the International Association for the Study of Pain (IASP) who define pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage… pain is always subjective. Each individual learns the application of the word through experiences related to injury in early life” (Merskey 1991). By this definition pain is not part of an objective stimulus but is a part of subjective experience.

Much pain research has been motivated by efforts to combine the objective and subjective or to understand subjective experience in terms of objective responses to stimulation. Many of the non-painful tactile perceptions we feel, for example, originate from the activation of mechanoreceptors that have a distinct structure. The Pacinian corpuscle, for example, is shaped like a bean and layered like an onion. This structure enables the Pacinian corpuscle to detect changes in pressure and the fibres Pacinian corpuscles give rise to rapidly adapt to facilitate responses to changing pressure. Painful touch typically involves a mechanical stimulus that exceeds a noxious threshold or includes a noxious component such as excessive heat. Unlike the mechanoreceptors, nerve endings that transmit noxious information are naked and lie free in the skin. Thus they are known as free nerve endings and they arise mostly from the peripheral termination of Aδ (pronounced: A-delta) and C fibres. The free nerve endings are polymodal and can respond to non-noxious and noxious temperatures or mechanical stimuli.

When activity in Aδ and C fibres gives rise to pain or behaviour associated with pain then they are labelled as nociceptors. Fibres that only respond in the noxious range are labelled as nociceptive-specific while those that respond across the noxious and non-noxious range are labelled as wide dynamic range. There is considerable controversy as to whether nociceptive pathways code a single modality of pain or even if nociceptive pathways can be specifically associated with pain (Craig et al. 1995, Han et al. 1998, Wall 1995).

## Contents

* 1 Pain pathways
* 2 Pain without noxious stimulation
* 3 Pain interacts with touch
* 4 The definition of pain
* 5 Pain activates sensory and emotional areas of the brain
* 6 Closing the Cartesian divide
* 7 References

## [edit] Pain pathways

Figure 1: A schematic representation of how the thermal grill might produce an illusion of pain and illustrates the pathways described by Craig et al. Cool stimuli excite the spinothalamic pathway through the VMpo (purple), which subsequently inhibits the pathway through the MDvc (turquoise). In the thermal grill experiment both pathways are excited by the 20 oC stimulation (blue). The warm, 40 oC, bars (red), however, also inhibit the VMpo, but not the MDvc pathway, resulting in less excitation entering the inhibitory pathway. The net output is through the MDvc pathway to the anterior cingulate cortex resulting in the experience of a burning pain. Developed from Derbyshire (2002).

The primary afferent Aδ and C fibres terminate on neurons in the superficial dorsal horn of the spinal cord. Ascending projections to the thalamus originate from the most superficial layer, known as lamina I, and project contralaterally in the spinothalamic tract (STT). Intracellular recordings from lamina I neurons revealed neurons with seemingly modality-specific responses [add reference]. One class of neurons was nociceptive specific, responsive only to noxious pinch, heat or both. Another class was thermoreceptive-specific, responding only to non-noxious cooling. A final class was polymodal, responding to heat, pinch and cooling (HPC). Provocatively, the existence of lamina I neurons, with specific responses and distinct morphology, motivated the suggestion that there are dedicated pathways for pain and temperature detection (Han et al. 1998).

In a particularly elegant study, Craig and colleagues used the ‘thermal grill illusion’ to illustrate the potential influence of these pathways (Craig and Bushnell 1994). The thermal grill illusion is generated by interleaved bars of warm and cool placed against the skin. The subject should experience interleaved warm and cool consistent with the stimulus actually delivered, but typically the subject will report a burning cold that is painful.

Craig explains this illusion as the consequence of integration across multiply activated pathways. The cool bars activate both thermoreceptive cells, which respond to non-noxious cooling, and polymodal cells, which respond to heat, pinch and cooling. Under conditions of normal, non-noxious cooling, activity in the thermoreceptive pathway dominates and the HPC pathway is inhibited. The presence of the warm bars, however, complicates the situation. The warm bars do not affect activity in the HPC pathway but do inhibit the cool pathway. Consequently, the interleaving of warm and cool bars causes relative excitation in the HPC pathway and generates a painful burning cold. When Craig and colleagues used the thermal grill in conjunction with brain imaging they generated an experience of painful burning cold and demonstrated activity in the anterior cingulate, insula and secondary somatosensory cortex (Craig and Bushnell 1994). The proposed mechanism is illustrated in Figure 1.

The proposal of dedicated pathways for specific experiences, including pain, implies that there ought to be a one-to-one relationship between specific noxious stimuli and pain experience. This proposal is controversial because pain occurs quite frequently in the absence of specific noxious stimuli and pain experience is easily influenced by activation in other sensory modalities, especially touch.

## [edit] Pain without noxious stimulation

A significant number of patients have chronic unremitting pain in the absence of any identifiable injury or diagnostic marker. Such patients include those suffering from low back pain, fibromyalgia, irritable bowel syndrome, atypical facial pain and a number of other disorders that can be loosely grouped under the category of ‘functional disorders’ (Barsky and Borus 1999, Wessely et al. 1999). These disorders are considered ‘functional’ because they can only be diagnosed following the report of symptoms rather than via an objective diagnostic test. Despite the lack of objective indicators, functional pain reduces quality of life, generates considerable health care costs, decreases work-related productivity and may increase mortality (Inadomi et al. 2003, Maetzel and Li 2002, McFarlane et al. 2001).

The persistence, intractability and apparent absence of peripheral disease to account for functional pain has led to an increasing interest in the neuropsychological mechanisms that might underpin functional pain. A series of studies have now demonstrated that pain can be generated in normal volunteers without the presence of a stimulus that could cause tissue damage. For example, participants report pain in the absence of a stimulus more readily after viewing images of other people in pain and a significant minority report pain directly associated with the image (Kirwilliam and Derbyshire 2008, Osborn and Derbyshire 2009). Participants reporting pain when viewing an image of someone else in pain activate the anterior cingulate, insular and somatosensory cortices (Osborn and Derbyshire 2009). Highly suggestible participants can also be induced to experience pain without a noxious stimulus under hypnosis and also activate the anterior cingulate, insular and somatosensory cortices (Derbyshire et al. 2004).

## [edit] Pain interacts with touch

Anyone who has ever had a mild injury will know that rubbing the area tends to reduce the experience of pain. This simple observation demonstrates that pain and touch must sometimes interact. Over 40 years ago, Melzack and Wall proposed that the interaction of pain and touch begins in the dorsal horn where touch fibre terminations presumably connect with cells transmitting noxious information and damp the flow of noxious activity (Melzack and Wall 1965). Melzack and Wall reasoned that the cells of the spinal cord, which first receive incoming information, must select and compute outputs based on the combination of signals received. A descending influence upon these cells from the brain was also included, which in turn was influenced by input from the spinal cord cells, thus forming a spinal cord-brain loop. Although Melzack and Wall’s gate control theory is no longer considered correct in detail it is still widely quoted for its heuristic value (Sufka and Price 2002). Importantly, gate control theory shifted attention away from the peripheral source of injury and towards the spinal cord and brain. It also made it difficult to argue that pain is a direct consequence of activity in a dedicated ‘pain pathway’. The gate control theory also stimulated the treatment of pain as a symptom or problem in itself, independent of any clinical diagnosis. After all, if pain cannot be reliably judged following an objective measure of injury or receptor activation, then assessment of pain must fall to subjective factors.

## [edit] The definition of pain

The importance of subjectivity in pain is captured by the IASP definition of pain referenced at the beginning. Although heavily criticized and debated (Anand and Craig 1996, Derbyshire 1999), the IASP definition remains largely accepted by those that research and treat pain. The IASP definition is important because it shifts attention away from the stimulus and towards the experience of pain. We cannot rely on the stimulus to provide a clear indication of experience because subjectivity does not exist in the stimulus; subjectivity exists in the person responding to the stimulus. The IASP definition reminds us that pain is subjective and that the content of pain subjectivity includes both sensory and emotional factors.

## [edit] Pain activates sensory and emotional areas of the brain

Consistent with the multidimensional nature of pain, brain imaging studies demonstrate that pain experience correlates with activity in both sensory and emotional regions of the brain (Apkarian et al. 2005, Derbyshire 2000). Noxious stimuli consistently activate primary and secondary somatosensory cortices, which presumably code the intensity, location and other sensory factors associated with the stimulus. Noxious stimuli also consistently activate the anterior cingulate, insular and prefrontal cortices, which presumably code the unpleasantness and cognitive components associated with the stimulus. Rainville and colleagues used hypnosis to dissociate the sensory and emotional components of pain and demonstrated greater activation of the anterior cingulate cortex when pain unpleasantness was increased via hypnotic suggestion (Rainville 1997). Activation in primary sensory cortex (S1) was unaffected. A further study demonstrated increased S1 activity when pain intensity was increased via hypnotic suggestion (Hofbauer 2001).

## [edit] Closing the Cartesian divide

The fact that both sensory and emotional components of pain can be influenced by hypnosis, and that pain can be generated directly by hypnosis and other types of suggestion (Osborn and Derbyshire 2010, Derbyshire et al. 2004), highlights the fact that pain experience involves more than stimulation of neurons in the skin. Pain is something consciously active; a product of minds rather than physics. Descartes explained long ago that while the mind is clearly exposed to sensory information, the mind is not drowned or dissolved by the senses (Descartes 1641). Human beings are self-located within sensory experience but we are not sensorily immersed; our intuition of ourselves as particular things with particular location and experience is opened up by, rather than collapsed into, our senses.

There is tension between pain as a physical, or objective, reaction and pain as a subjective experience (Grahek 2007). There is a temptation to reduce pain to its physical, raw, nature by stripping away the layers of conceptualisation that we associate with knowledge. The challenge is to understand pain as something apprehended rather than comprehended. Pain, at some primitive, raw level just is.

Pain that just is, immediate and without further elaboration, might presumably be the product of activity in dedicated pathways that process stimuli in the noxious range. Once activity in those pathways reaches a critical threshold then pain will be registered for all sentient beings in roughly comparable fashion. In more complex, conscious, beings such as humans, that initial immediate experience will be taken up and elaborated through a nexus of knowledge. Understanding pain as a part of knowledge means taking account the whole complex of traits by which we are characterised (Mannheim 1935). The very fact that pain is experienced as something multidimensional but separate from other experiences implies the existence of a conceptual apparatus that can marshal the dimensions of pain into a coherent experience. It is no longer possible to experience pain as a raw, pure, apprehension, pain can only be experienced as an elaborated comprehension. There is no return to innocence once pain is marshalled into knowledge. And even though dedicated pathways for noxious information remain a part of the story, they cannot be isolated from the broader neural and informational influences over pain. Pain does not have primacy over subjectivity, existing before and in addition to subjectivity, but is now experienced through subjectivity. That is what makes painful touch so interesting and maddeningly capricious.

## [edit] References

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