Bonnie D. Wright MistralVet, Johnstown, Colorado, USA Treatment of pain, both the acute self‐limiting and especially the longer‐duration or ongoing varieties, greatly benefits from therapies that alter the body’s potent homeostatic and neuroimmune modulatory capacity. Non‐pharmacologic therapies target the extensive and effective endogenous analgesic systems housed within the nervous system as well as the myofascial system. Understanding the physiology of neuroimmune and fascial modulation facilitates applying discrete therapies to augment the pharmacologic treatment of pain conditions. These therapies may be machine‐based, practitioner‐applied, or self‐applied through directed forms of motion. Although most of these therapies lack the research base of pharmacologic therapies, they are firmly rooted in the science of physiology, and are potent tools for comprehensive treatment of pain in veterinary medicine. Physiology provides a complex, multifaceted tapestry for both pain sensing and modification of transmitted signals. Non‐pharmacologic interventions for the treatment of pain interface with these pre‐existing structures and receptors in many of the same ways as pharmaceuticals, including but not limited to endogenous opioids, 5‐hydroxytryptamine, glutamate, norepinephrine (noradrenaline), dopamine, γ‐aminobutyric acid, endocannabinoids, acetylcholine, and purines [1]. Understanding the physiology of nervous system wiring, which is reviewed in Chapter 46, is the first step toward understanding methods to intervene in these endogenous systems and help modify them toward homeostasis. In addition to modification of pain, there is overlap between the nervous system and other endogenous, homeostatic systems such as the immune state, gastrointestinal motility and enteric control, vasomotor tone and fluid balance, and hormonal and reproductive balance [2–4]. Due to their global (entire organism) effects, non‐pharmaceutical therapies often have overlapping actions on several homeostatic systems. The database for non‐pharmacologic treatments is rapidly expanding in the wake of scientific discovery and the response to the human opioid epidemic [5,6]. At the time of writing, the most researched and accepted techniques of non‐pharmacologic pain control can be grouped into those that influence peripheral cutaneous sensory tissues through delivery of energy (light or acoustic) or sensory stimuli [7], those that modify central (spinal and supraspinal) neurotransmitters, including modulation of vagal activity and other components of the autonomic nervous system [1,8,9], and those that utilize the physiology of mechanosensitive tissues to elicit physiologic changes [9,10]. Most modalities work through a combination of these mechanisms. In addition to provision of non‐pharmacologic therapies to patients, compelling data suggests their overall metabolic state is also important. Obesity is a proinflammatory state, and there is strong evidence that appropriate body condition is integral to pain control [11]. Similarly, dietary management may reduce proinflammatory products, and administration of omega‐3 fatty acids may reduce inflammatory states in dogs [12]. Temperature‐related modalities, such as application of ice and heat, work primarily through peripheral cutaneous sensory tissues and transient receptor potential (TRP) channels [7]. Other sources of peripheral cutaneous tissue modulation include acupuncture, massage, stretching, photobiomodulation, electromagnetic therapies, and extracorporeal shockwave therapy (ESWT). While much focus is placed on the nociceptive role of cutaneous innervation, it is important to note that many peripheral analgesic modalities also work through sensory receptors other than nociceptors, which underlies the importance of touch in the treatment of pain [13]. Applying cold to skin decreases temperature up to a depth of 2–4 cm. This results in decreased activation of tissue nociceptors and slows conduction velocity along peripheral axons (cold‐induced neuropraxia) [14]. Specific cold‐sensitive ion channels, TRPM8 channels, contribute to analgesia by decreasing signaling through other pain‐sensitizing channels as well as reducing incoming painful stimuli via central inhibitory interneurons [15]. Cold therapy also decreases edema formation via sympathetically mediated vasoconstriction and decreased delivery of inflammatory mediators to injured tissues. Another contribution to pain relief comes from reduced muscle spasms. Cold applied directly to muscles inhibits the motor reflex loops that maintain contraction and spasticity, thereby reducing the latter and relieving muscle spasms [16]. Muscle spasm may be present in patients with both acute and chronic pain and is a major cause of discomfort [14]. Ice is generally considered for acute injuries (up to three days postoperatively or postinjury) but, due to its analgesic effects, may also be used long term [7]. Unlike coolness, heat (or chemical mediators such as capsaicin or ginger) is not considered directly analgesic at the level of nerve endings but, because it increases blood flow and collagen distensibility (which reduces stiffness), it may provide some analgesia [17]. TRPV1 channels on afferent nerve endings sense heat. This can result in a proinflammatory or anti‐inflammatory state via interleukin (IL)‐6 in muscle tissue [18]. In general, heat is used more frequently for chronic conditions associated with fibrous or musculotendinous restrictions, or to help drain edema after it has formed which usually occurs on approximately the third day after an injury [17]. Acupuncture and related therapies utilize discrete neuroanatomic points on the body. These have effects in each of the three physiologic pathways described in this chapter: neuromodulation at peripheral, spinal, dorsal root ganglion, and supraspinal levels; myofascial mechanotransduction; and temperature‐related changes. The cutaneous sensory system is critical to efficacy, as many studies have shown that these effects are abolished by local anesthetic drugs [19]. Most recognized acupuncture points are anatomically rich and characterized by myelinated and unmyelinated nerves, low‐threshold mechanoreceptors (LTMRs), fibroblasts and the collagen matrix, mast cells, and microcirculatory complexes [20]. Needle placement causes direct nerve stimulation as well as secondary stimulation through mechanical forces applied to the fascia and cellular milieu in the region surrounding the point. It has long been recognized that acupuncture points are found in cutaneous regions that show high levels of diverse innervation [20]. This occurs where groups of nerves emerge through bone, muscle, and fascia from their origins, where they branch or join, and where they attenuate distally. These nerve fibers are made up of Aβ and Aγ (myelinated) and C (non‐myelinated) fibers, as well as autonomic fibers; acupoints generally have greater neural density compared to non‐acupoint regions [21]. In general, myelinated somatic sensory fibers are most prevalent near acupuncture points, with most being Aβ and Aγ fibers, except in strong motor or Golgi tendon points. While there is often a focus in acupuncture research on the modification of high‐threshold (HT) pain‐sensing nerve types, it is likely that LTMRs play an important role in this modality [13]. Acupuncture needle sensation is seldom painful, and many of the sensations typically associated with acupuncture (such as warmth, coolness, pressure, and movement) are probably associated with LTMR activation and the engagement of TRP channels, rather than nociceptor activation. These peripheral components, which are located in the skin and along peripheral nerve bundles, help explain why neuromodulation is the primary mechanism mediating acupuncture analgesia. Acupuncture stimulates afferent nerve fibers, and this has been demonstrated with manual acupuncture as well as with electroacupuncture. Both manual and electrical forms of stimulation activate all four types of nerves, Aα, Aβ, Aδ, and C fibers, although at unique discharge frequencies [22].
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Non‐Pharmacologic Management of Pain
Introduction
Physiology of non‐pharmacologic pain medicine
Peripheral cutaneous sensory receptors
Temperature‐related modalities
Acupuncture – peripheral neuromodulation
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