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178 Section 3 / Nonpharmacological Pain Therapy neural excitation. Interestingly, mechanical displacement of
con-nective tissue creates a shear wave, which is much greater when needles are placed in acupuncture points rather than in nearby sham (nonacupuncture) points. Calcium ion channels and adeno-sine are subsequently activated (Yang et al., 2011). Acupuncture points also contain sympathetically innervated small blood ves-sels, lymphatics, fibroblasts, lymphocytes, and platelets. These cells release neurotransmitters and inflammatory and immunomodula-tory factors (Zhang et al., 2012). Factors that inhibit afferent fibers include: acetylcholine, norepinephrine, GABA, -endorphin, SP, somatostatin, nitric oxide, ATP/cGMP, and adenosine. Stimula-tory mediators released include: various cytokines, prostaglandins, bradykinin, glutamate, and many others. Serotonin and histamine can be either excitatory or inhibitory depending on which receptors they are acting upon. The predominant effect of acupuncture in pain conditions is to enhance the activity of inhibitory mediators (Hurt & Zylka, 2012).
Spinal and Supraspinal Mechanisms
Through the last decade, studies on neural mechanisms underlying acupuncture analgesia have focused on the cellular and molec-ular substrates involved. Diverse signaling molecules and recep-tors contribute to acupuncture analgesia, including opioid peptides (, ␦, and receptors), glutamate (NMDA and AMPA/KA receptors), 5-hydroxytryptamine (serotonin), and cholecystokinin-8 (CCK-cholecystokinin-8). Whereas CCK-cholecystokinin-8 antagonizes acupuncture analgesia, opioid peptides and their receptors in the spinal dorsal horn play a pivotal role in mediating acupuncture analgesia. The release of opioid peptides evoked by electroacupuncture is frequency-dependent. Electroacupuncture at 2 Hz and 100 Hz cause the release of enkephalin and dynorphin in the spinal cord, respectively.
Evidence also exists for spinal microglial involvement in the antinociception of electroacupuncture (Zhao, 2008). Analgesic effects may be associated with inhibition of spinal glial activa-tion, and thereby provide a potential strategy for the treatment of arthritis or other inflammatory conditions.
Several spinal and supraspinal areas are involved in acupunc-ture analgesia (Bowsher, 1998). The trigeminal, spinothalamic, and spinoreticular tracts receive afferent signals from their respective receptive fields and transmit the information to subcortical and cor-tical areas. The dorsal column may also have an important role in modulation of acupuncture effects, particularly in regulating vis-ceral functions (Chen & Ma, 2003). Mechanoreceptor-activated signals are believed to be the dominant components of afferent impulses from the majority of points, and the dorsal column-medial lemniscus tract receives sensory information from multiple sources, including cutaneous pain and visceral sensations in addition to fine touch and proprioception.
Many brain regions are affected by acupuncture, and imaging studies demonstrate heterogeneity of response rather than a soma-totopic representation of points. This widespread and diverse mod-ulation of brain activity that occurs with acupuncture is most likely related to the multiple central pathways that are affected by point stimulation.
Multiple brain nuclei, composing a complicated network, are involved in processing of acupuncture stimulation, including the nucleus raphe magnus, periaqueductal gray area, locus coeruleus, arcuate nucleus, preoptic area, nucleus submedius, habenular nucleus, accumbens nucleus, caudate nucleus, septal area, and
amygdala. Most of these nuclei are constituent parts of the endogenous descending inhibitory system, with serotonin and catecholamine-containing neurons projecting to the spinal cord (Li et al., 2007; Zhang et al., 2011; Zhang et al., 2012).
Neural Networks
Neural networks, very similar to pattern generators, are groupings of facilitated pathways that need very little input or control after initiation to create a complex physiological or motor response.
Acupuncture, and especially electroacupuncture, may have global central nervous system (CNS) impact by altering the neural net-works. Functional MRI studies provide an integrated view of the specificity of dry needle acupuncture, with needle sensation and the subsequent neural cascade contributing to a reconfiguration of complex neural networks (Faingold 2008; Qin et al., 2011).
The neuronal network that serves acupuncture analgesia is thought to activate structures of the descending inhibitory pathways and deactivate limbic structures within the ascending nociceptive pathway (Campbell, 2006).
Acupuncture is a slow-acting modality, and changes in the neural connectivity continue to occur for a prolonged period after needles are applied. Liu et al. (2010) describe time-varied characteristics of acupuncture on distinct brain networks. This is consistent with the observation of a continuing effect over days, and even longer, after acupuncture.
MERIDIANS
Many of the bioactive acupuncture points are considered to lie along anatomically described lines. The points on a meridian have com-mon functions and are thought to communicate. Observations sup-porting the existence of meridians include: changes of impedance, thermal and sense propagation, radioisotope uptake, and light and sound wave transmission (Yan et al., 1992). There is some thought that meridians follow lymphatic flow. It has also been suggested that electrical conductance follows Bonghan channels, which are threadlike tissues that have been found floating in blood and lymph vessels and covering organs. Their presence has been confirmed in lymph vessels with the use of magnetic nanoparticles (Johng et al., 2007). Others have suggested that the meridians might be a func-tional, rather than an anatomical, concept that includes the nervous, circulatory, endocrine, and immune systems (Zhao, 2008).
CLINICAL PRACTICE OF ACUPUNCTURE
In clinical practice, acupuncture treatment regimens generally use multiple points located in different parts of the body. Empirical and experimental evidence suggests that the combination of local and distant points produces greater treatment effects than the use of sin-gle points. Simultaneous stimulation of different points appears to elicit a more widespread and intense regional brain response (Zhang et al., 2012). Given that superior therapeutic response appears to be associated with synergistic or additive effects of point stimulation at local and distant sites, the clarification of this relationship will provide valuable information in the development of more efficient acupuncture treatment regimens.
Increasingly, clinical veterinary studies demonstrate the effec-tiveness of acupuncture. A return to function has been described in a cat with multifocal disc disease (Choi & Hill, 2009). Another
16 / Mechanisms of Acupuncture Analgesia 179 study describes electroacupuncture as the sole analgesic required
for bovine surgery (e.g., caesarian section, rumenotomy) (Kim et al., 2004). In a clinical study of dogs with intervertebral disc disease and long-standing severe neurological deficits, acupunc-ture treatment alone was reported to be superior to surgery alone (Joaquim et al., 2010). Acupuncture treatment combined with West-ern treatment in dogs with thoracolumbar disease and no deep pain was superior to Western treatment alone for return to ambulation (Hayashi et al., 2007). The return of deep pain was not signifi-cantly different between the two groups; however, three out of six dogs receiving acupuncture, and one out of eight dogs not receiv-ing acupuncture, had an acceptable return to function. Laim et al.
(2009) reported that electroacupuncture initially improved analge-sia, though less so after the first 12 hours, when applied adjunctively post surgery to dogs undergoing hemilaminectomy. Shorter time to ambulation and deep pain perception occurred in dogs with thora-columbar intervertebral disc disease when Western treatment was combined with electroacupuncture (Han et al., 2010). Gold bead acupuncture in dogs with hip dysplasia was reported to improve mobility and lessen pain scores for at least 2 years (Jaeger et al., 2006, 2007). Bilateral stimulation of acupuncture points induced a shorter latency period, greater intensity, and longer duration of analgesia in dogs subjected to thermal and mechanical nocicep-tive stimuli (Cassu et al., 2008). Preoperanocicep-tive electroacupuncture (EA) provided better post-ovariohysterectomy analgesia than did butorphanol in dogs (Groppetti et al., 2011), though not in horses with rectal distention (Skarda & Muir, 2003). Dogs treated with EA had a reduced need for postmastectomy rescue analgesics than did dogs treated with morphine (Gakiya et al., 2011). Peri-incisional treatment with transcutaneous electrical stimulation at acupuncture points, as opposed to nonacupuncture points, decreased the initial postovariohysterectomy pain scores, and decreased the dose of res-cue analgesics needed in dogs (Cassu et al., 2012). Electroacupunc-ture improved lameness scores and increased serum-endorphin concentrations in an experimental equine lameness model (Xie et al., 2001). Multiple sessions of EA was reported to be supe-rior to phenylbutazone for treating horses with chronic back pain (Xie et al., 2005).
Modes of Therapy
Several methods of stimulation of acupuncture points can be employed, and traditionally each has a different purpose. A ses-sion typically lasts for 30 minutes, during which needles are inter-mittently rotated, electrically stimulated, or in some cases, heated.
The needling sensation, known as de-qi (pronounced “day-chee”), is a predictor of acupuncture analgesia in human patients (Leung, 2012). It entails a sharp pricking sensation, but is also reported as a dullness, heaviness, deep ache, numbness, or flooding warmth. In animals, it is manifested by a strong response to the needle followed by a sudden relaxation.
Dry Needle
The most common veterinary application is to apply needles alone to acupuncture points. A subsequent de-qi response, such as a strong reaction, local hyperemia, or sudden sedation, signifies that the point has been located. The angle and depth of insertion vary with the anatomical location, age, size, and health of the patient. Moving the needles with a gentle thrust in a clockwise direction is tonifying (strengthening), and moving the needle with a forceful thrust and
twisting counterclockwise is sedating, and is used to diminish an excessive physiological state. Duration of needle stimulation is commensurate with the needs of the animal.
Aqua Acupuncture
Fluid may be injected into acupuncture points to prolong the effect of point stimulation. Practitioners use various substances includ-ing saline, vitamin B12, and AdequanR. Bee venom injected at acupuncture point ST36 potentiated analgesia in neuropathic pain states in rodent models (Yoon et al., 2009), and is used in some TCVM practices. Autologous blood is used in acupuncture points for an anti-inflammatory effect. Injection into acupuncture points is quick, and can be used in animals that do not tolerate prolonged needling or EA.
Laser Acupuncture
Laser-emitting diode devices can be used to stimulate acupunc-ture points. Low-power (5–30 mW) energy of wavelengths 630–
960 nm is common in veterinary medicine. Laser has been shown to be analgesic and anti-inflammatory (Lorenzini et al., 2010). Laser light refracts within 15 mm in tissue, so it is useful for shallow acupuncture points, or in areas of thin integument. More powerful lasers are being developed, and may become useful in veterinary acupuncture.
Material Implantation
Acupuncture points can be stimulated over a long period of time by inserting various materials including: surgical suture, skin staples, or gold beads or wire. The most common technique is to implant gold periarticularly in animals with hip dysplasia or degenerative joint disease. Gold bead implantation is reported to be associated with diminished pain and increased ambulation, but variable results have been reported (Jaeger et al., 2006, 2007).
Electroacupuncture
Applying electrical stimulus to peripheral nerves through percu-taneously placed needles can produce prolonged analgesia lasting from hours to days or longer. This form of acupuncture is commonly applied to animals. Electric frequencies are usually set anywhere from 1 Hz to 200 Hz, and the millivoltage is set such that the animal barely notices it.
Electroacupuncture results in the release of endomorphin, dynor-phin, enkephalin, and-endorphin (Lin & Chen., 2008), and is an effective method shown to attenuate inflammatory, neuropathic, and cancer pain. Many neurochemicals, in particular endogenous opiate peptides, 5-HT, and catecholamines, exhibit a frequency-dependent release during EA. Though there is inconsistency in study results, different analgesic mechanisms have been demonstrated with high-and low-frequency stimulation. High-frequency (80–120 Hz) elec-trical stimulation at local points is recommended for segmental inhibition, and is associated with the release of dynorphins, sero-tonin, and GABA. Low-frequency (0.5–20 Hz) stimulation is more effective at remote sites for a more diffuse systemic effect, and is associated with the release of endorphins (Xing et al., 2007). Of note, alternating frequencies between 2 Hz and 100 Hz will cause a release of a full spectrum of endorphins (Wang et al., 2008).
In contrast to Xing et al. (2007), White et al. (2008) reported that high-intensity, but not low-intensity, EA applied unilaterally generates a significant and persistent bilateral hypoalgesic effect.
180 Section 3 / Nonpharmacological Pain Therapy The underlying mechanism of long-term synaptic alterations is still
unclear, but the NMDA receptor is involved. It seems that low-frequency stimulation (2 Hz) results in subsequent diminishment of neuropathic pain that relies on NMDA receptor stimulation to depress C-fiber evoked potentials in the dorsal horn (Xing et al., 2007). This is counter to the widely held belief that the NMDA receptor must be antagonized in the resolution of chronic pain. It is possible that the activity of this receptor plays a role in modulation of neurotransmission through depression as well as potentiation.
Higher frequencies, such as 100 Hz, seem to be dependent on GABAergic and serotonergic inhibitory pathways, and seem to be less effective in diminishing neuropathic pain than the lower frequencies.
Hypothalamic neuroendocrine functions are also affected. Imme-diate and repeated electroacupuncture normalized behavioral and biochemical abnormalities in various models of animal stress, including immobilization, maternal separation, chronic mild stress, surgical trauma, chronic administration of corticosteroids, cold stimulation, tooth-pulp stimulation, and mechanical colon disten-tion (Zhang et al., 2012).
CHRONIC PAIN
Although some acupuncture procedures are effective in acutely terminating signs, it is often necessary to use a repetitive protocol to achieve full therapeutic effect, particularly with chronic pain.
This may be, in part, due to a cumulative effect needed to produce a persistent CNS change.
Treatment of chronic pain usually requires the use of local points, segmental points, and points with an autonomic effect; points related to tissue and structural compensation, such as trigger points, or myofascial origins or insertions often distant to the location in question. Table 16.1 briefly lists basic examples of points that can be added to an analgesic protocol.
Recent work has looked at the effect of acupuncture in hyperal-gesic, allodynic, and neuropathic animals. Acupuncture can dimin-ish the sensitization and CNS changes that are pivotal to the development of neuropathic pain. Acupuncture has been shown consistently to minimize or prevent neuropathic pain in animal models, and electroacupuncture as well as laser stimulation of
Table 16.1. Common acupuncture points used for variable pain states and locations
Pain state and location Common acupuncture points used
Inflammation LI4, GV14, LI11
General pain LIV3, GB34, BL60, GV20, SP6 Neuropathic pain ST36, PC6, TH5
Bone and arthritic pain BL23, KID1, KID3, BL11 Neck pain Jing Jia Ji, SI3, BL23, BL24,
BL25
Hip pain GB27, GB28, BL54, Jian-Jiao
Elbow pain SI8, PC3, HT1, LI11, LU5
Back pain Hua-tuo Jia Ji, Bai Hui, Shen Shu, BL40
points appears to be effective. In a study of irritable bowel syn-drome in rats, a form of visceral neuropathic pain, treatment with ST 36 and ST 37, but not gall bladder (GB) points, was effective in diminishing pain and gut pathology (Tian et al., 2008). Elec-troacupuncture of low frequency at ST 2 has been shown to confer analgesia in a visceral pain model in rats, and in human patients with trigeminal neuralgia.
It is important to NOT needle the affected area when treating neu-ropathic pain if an autonomic component is suspected, because the needle stimulation can cause excruciating allodynic pain. Needling surrounding affected areas is helpful, as is treating the underly-ing pattern with TCVM principles. For specific local effect, treat-ing the segmental paravertebral association and Hua-tuo Jia Ji points is beneficial. The literature suggests that for significant neu-ropathic pain reduction to occur, at least five biweekly sessions are necessary.
Trigger Points
Trigger points (also known in TCVM as Ashi points) commonly develop subsequent to postural changes occurring secondary to painful states, such as osteoarthritis. Trigger points, small firm painful foci within a muscle belly, are traditionally treated by a dispersing and sedating needle technique, moxibustion, deep acu-pressure massage (tui na), cupping (in humans) or rubbing. Nee-dles can be inserted just until the “gummy” feeling is contacted.
Sometimes a trigger point needs to be needled deeply, and with a pecking motion, to reflexively relieve the spasm. Needles are left in for varying periods, between a moment and 60 minutes. Dispers-ing and sedatDispers-ing techniques vary in the literature, but this author tends to use techniques of counterclockwise, and fast pecking inser-tion. Occasionally, simply placing the needle will be sufficient to cause relaxation of the trigger point and normalization of the area.
Then the needle can be immediately removed. Once the trigger point is treated, systems become functional again: often lymphatic drainage, venous transport, arterial circulation, neural conduction, and regulatory and immune function can resume. See Chapter 14 for a more detailed discussion of trigger points.
Visceral Pain
Acupuncture can be useful in patients with functional GI disor-ders because of its effects on GI motility and visceral pain (Taka-hashi, 2011). Commonly, pain is referred to axial or extremity muscles, creating regional trigger points. Similar regional trigger points resulting from other causes can look identical to visceral pain-induced trigger points. Therefore, visceral disorders are part of the differential diagnosis of regional trigger points.
Cancer Pain
Acupuncture analgesia is an adjunctive treatment for patients with cancer pain. Control of pain and local swelling postoperatively, shortening the resolution of hematoma and tissue swelling, and minimizing use of medications and their attendant adverse effects, are reasons to utilize acupuncture for cancer management. In a Sloan–Kettering study of radiation mucositis, a neuropathic state following upper body radiation, 39% of 70 head and neck cancer patients demonstrated an improvement when treated with acupunc-ture compared to a 7% improvement of patients treated with phys-ical therapy (Pfister et al., 2010). Zhang et al. (2012) demonstrated in rats that acupuncture can counteract the cancer-driven expression
16 / Mechanisms of Acupuncture Analgesia 181 of the transient receptor potential vanilloid 1, thereby attenuating
cancer pain.
Bone pain in cancer is a predominant issue. One study involving a rat model for bone cancer pain (Zhang et al., 2008), reported that electroacupuncture over the sciatic nerve (at acupuncture point GB 30 (Huantiao)) significantly attenuated cancer-related hyperalgesia and the expression of dynorphin and interleukin-1beta (IL-1).
SUMMARY
Acupuncture is a complex intervention that has been used clinically for thousands of years to reduce pain in a variety of disease states.
The physiological mechanisms underlying analgesia produced by acupuncture are being defined. In the meantime, practitioners of both traditional and Western forms of acupuncture can offer patients relief from suffering.
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