Common sources of neurological amplification: nociceptive fibres.
According to the International Association for the Study of Pain (IASP), pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” This definition contains two important agreements that comprise the foundation of understanding pain syndromes: First, that pain is a conscious experience (i.e. psychological and therefore by definition a brain event), and second, that this brain event may or may not be associated with detectable tissue damage anywhere in the body – although it is, also by definition, usually felt as if it was associated to tissue damage.
Regarding this last point, and again according to IASP: “…many people report pain in the absence of tissue damage or any likely pathophysiological cause; usually this happens for psychological reasons. There is usually no way to distinguish their experience from that due to tissue damage if we take the subjective report. If they regard their experience as pain, and if they report it in the same ways as pain caused by tissue damage, it should be accepted as pain. This definition avoids tying pain to the stimulus. Activity induced in the nociceptor and nociceptive pathways by a noxious stimulus is not pain, which is always a psychological state, even though we may well appreciate that pain most often has a proximate physical cause.”
This paragraph suggests that psychological is a realm separated from neurological, which is not compatible with contemporary science and neurophysiology.
Despite Descartes insistence in separating reality into the res cognitas (consciousness, mind) and the res extensa (matter, extension), and impregnating Western philosophy for more than 300 years with his intellectually appealing, but inaccurate concept of dualism, we know now that there is no such a thing as a mind separated from the matter responsible for the phenomena of consciousness and emotions (i.e. the human brain as well as the brain of other animals).
At one time, dualism allowed for the separation of sciences and the non-physical realm (allowing scientists to conduct their research without fear of being considered heretics by religious groups). Nowadays, dualism creates a serious problem for anybody approaching the study of mind-related events, such as the aforementioned pain syndromes. Interestingly, it was Descartes himself, in his famous 1637 Discours de la Méthode, who advocated the systematic doubting of knowledge, believing that sensed perception and reason deceive us and therefore, man cannot have real knowledge of nature. The only thing that he believed could be certain was that he was doubtful, leading to his famous phrase Cogito ergo sum: I think therefore I am – which, in an updated version relevant to our subject today, it could read “I doubt, therefore I am scientific.”
This may seem philosophical, but it is highly relevant to the topic because as I have just demonstrated, science in general and pain medicine in particular are still impregnated with the biases of past centuries, which in turn are conditioning the way we see and treat these pain problems in everyday clinical practice. To help clinicians with an updated approach to the management of pain problems, we must discuss the many possible contributors of a complex pain experience. Because pain is a brain event and all brain events are by nature the product of non-linear physiological processes, they are therefore complex. We seem to have failed so far in pain medicine because of the use of linear models, mostly structure based, that simply cannot explain the observed non-linear behaviour of these complex clinical problems.
As a complex central nervous system by-product, where sensory, cognitive and emotional contributors are all part of the unpleasant experience, pain is deemed to have numerous physiological contributors that I’d like to call“pain contributors.” Obviously, the pathophysiology of pain contributors is complex and not fully understood, and it may involve “up regulatory” and “down regulatory” mechanisms on the nociceptive pathways, including phenomena such as peripheral and central sensitization, silent nociception, and neuronal plasticity. Also related to the neurophysiology of inflammation, sympathetic nervous system hyperactivity is known to be a majorcontributor to all pain problems.
Less understood contributors include dysfunction of pre- and post-ganglionic sympathetic neurons, abnormal visceral autonomic activity, lack of sufficient non-noxious information from these or adjacent segments related to the kinetic chain (proximal and distal joints, synergistic and/or antagonistic muscles, etc.). It is even possible that any nociceptive signal from any innervated tissue, regardless of topographic location, could become a source of amplification in a given pain problem.
Practitioners of pain medicine need to be able to evaluate and identify these common contributors to pain syndromes. Being able to provide a timely, relevant treatment to optimize functional recovery requires a systematic, yet holistic approach. A practical neurofunctional treatment model (See: “The neurofunctional era: Optimizing the use of therapeutic resources” on Canadianchiropractor.ca) will be best to help practitioners select the most appropriate neuromodulatory interventions for the most relevant levels involved in each pain problem.
For the sake of making this discussion as clinically relevant as possible, a hypothetical elbow pain problem has been selected to illustrate the discussion, and an accompanying diagram (below) has been provided to reflect the 10 kinds of contributors to the pain experience, visually. Discussion of each contributor is signalled with the same number used in the diagram.
1. Local contributors: nociceptive fibres with receptor fields on dermatomal, myotomal, and sclerotomal tissues
Nociception is a neurological segmental phenomenon related to peripheral nervous system and spinal cord activity. Nociceptive signals are generated in response to chemical, mechanical and thermal stimuli acting over free nerve endings (belonging to C fibres and A-delta fibres) located on dermatomal, myotomal or sclerotomal structures.
These C and A-delta fibers are functionally referred to as nociceptive fibers, because of their ability to inform the central nervous system (CNS) about noxious stimuli, i.e. potentially harmful or unpleasant stimuli, whether there has been already tissue damage or not. These are the only nerve fibers capable of detecting noxious activity in the tissues, and to convey it to the CNS. These nociceptive signals are first processed at the dorsal horn of the spinal cord, and then carried to the brain stem, the thalamus, and other brain areas where they will be consciously perceived as pain.
While not all pain experiences originate on peripheral nociceptive signals, most pain experiences are contributed to by nociceptive activity, overt or silent.
Let’s remember that different sensory stimuli in the periphery of the body are detected and conducted by different receptors associated to particular type of nerve fibres. Each kind of sensory signal is processed differently at the spinal cord and at supraspinal levels.
For instance, some neurons possess thick myelinated axons that end in specialized encapsulated receptors in the peripheral tissues, each type of receptor devoted to a particular type of sensory input (e.g. vibration, light touch, tension, angular velocity). These receptors can only be stimulated by the specific stimulus they are designed to codify for, and no amount of other stimuli, including the presence of terrible tissue damage, could ever make these neurons contribute to the messages that eventually will become a pain experience in the brain; for instance, even if someone burns alive by fire or in a bath of acid (I apologize for the crude example, it is provided just to illustrate the physiological point), all the horrible pain experienced as a result of the massive tissue damage, will be solely contributed by nociceptive fibres in the affected tissues. None of the encapsulated specialized receptors (mechanoreceptors, proprioceptors, extereoceptors) will contribute any signals.
Some facts about nociceptive fibres:
• Nociceptive fibres have their cell bodies on the dorsal root ganglia and their axons in the peripheral tissues ending as free nerve endings (C and A-delta fibres): skin, periosteum, arterial walls, joint surface, capsules and ligaments, meninges, tentorium and faux cerebelli, viscera, and nervi nervorum. They contain substance P (vasodilation, increase permeability of microvasculature, and inducing histamine release from mast cells), calcitonin gene-related peptide (CGRP), and somatostatin.
• Free nerve endings in skeletal muscle typically end in the adventitia surrounding arterioles, while the muscle fibres proper are not supplied with neuropeptide-containing free nerve endings – a fact that may explain the lack of pain in response to massive tissue destruction in muscular dystrophies in contrast with the increased sensitivity associated with chemical pain due to disturbances of microcirculation.
• Nociceptive fibre density along the length of the muscle seems uniform but it is higher in the peritendon while almost absent in the tendon tissue proper. Corollary, tendons are not a main source of nociceptive information.
• Nociceptive fibres’ depolarization requires either physiological stimuli (mechanical, thermal, chemical) or pathological (inflammation, ischemia, necrosis, or neuropathic behavior = peripheral/spinal sensitization).
• Although large myelinated fibres respond only to specific sensory modalities, under situations of intense peripheral stimuli involving inflammation, some large calibre sensory fibres may undergo a phenotypic change, such that they can now activate dorsal horn neurons by producing substance P. (Neumann S. et al. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons. Nature 1996;384-:360-364)
• Examples of nociceptive pain on deep somatic tissues of the musculoskeletal system that are difficult to characterize include:
Osteomielitis (bacterial, fungal, viral): From cursing with pain and fever on an acute standard presentation, to becoming painless on a chronic situation. This pain is usually worse with movement, can radiate to the chest, abdomen, or limbs, and the affected vertebrae are tender on palpation.
Osteoporosis: The pain is due to bone fractures (vertebrae, hip, wrist, humerus, tibia), and it also behaves mechanically like osteomielitis. Bone tumors: Severe pain due to neoplasic tissue invasion of bone.
Joint disease: Multiple pain mechanisms involved: inflammation (septic, crystal induced, immune reactions), joint effusion (increased intra-articular pressure), release of cartilage-derived macromolecules and calcium-containing crystals, irritation of periarticular structures and subchondral bone.
• Muscle pain syndromes: mechanical and chemical factors involved such as inflammation, ischemia, toxic necrosis, myofascial pain syndromes, or inflammatory myopathies such as polymyositis, dermatomyosistis and the polymyalgia rheumatica.
It is hard to argue that local nociceptors are the number one contributors to
This article was originally posted in the Canadian Chiropractor Magazine on April 2019.