Analysis on the neurological mechanism of acupuncture treatment in Idiopathic tinnitus based on the theory of“central plasticity”

Peng-Xi Zhang,Tong-Sheng Su

1Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,China.2Department of Acupuncture and Moxibustion,Shaanxi Hospital of Traditional Chinese Medicine,Xi'an 710000,China.

Abstract Recent studies have found that although tinnitus originates from the cochlea, its root lies in the plasticity of the auditory center.In other words, the peripheral auditory system damage causes abnormal excitement and even functional reorganization of the brain stem and cerebral cortex, finally leading to tinnitus progresses and persists in the center.The mechanism of "central plasticity" is related to the physiological characteristics of related brain regions, the characteristics of electrophysiological changes, the changes of central neurotransmitters, and psychological factors.It is speculated that the possible mechanisms of the acupuncture treatment of tinnitus are as follows: 1.Acupuncture can alter the level of neurotransmitters 5-HT and GABA in nerve center, that is, GABA increases and 5-HT decreases after acupuncture; 2.Acupuncture changes the wrong central pattern of the cerebral cortex caused by tinnitus through strong stimulation, and aids the cerebral cortex adapt to the changes of the internal and external environment to produce benign functional reorganization,in order to treat tinnitus;3.External stimulation of acupuncture can accelerate the contraction of muscle vessels around the ears, accelerate blood circulation and metabolism, and improve the blood supply of the auditory system, thus improving tinnitus.4.Acupuncture can improve or even cure tinnitus by stimulating the acupoint-nerve pathway around the ear,regulating unbalanced neurotransmitters, inhibiting abnormal nerve discharge, correcting wrong auditory pathway patterns,and establishing new auditory pathway nerve conduction patterns.

Key words: Central plasticity, Idiopathic tinnitus, Acupuncture, Electrophysiology, Neurotransmitters,Sphenopalatine ganglion,Acupoint-nerve pathway

Background

Tinnitus refers to the generation of one or more subjective sound perceptions [1] without external sound sources.Although classified into subjective and objective, experts have pointed out that objective tinnitus has sound sources in essence and does not meet the definition of tinnitus; therefore, all tinnitus is subjective tinnitus [2].In 2012, the expert consensus meeting referred to this kind of subjective tinnitus with no clear reason and no obvious abnormality detected by all kinds of medical equipment as idiopathic tinnitus[3].

It has been believed for a long time, that tinnitus may be related to the peripheral auditory system or ear microcirculation disturbance [4]; however, tinnitus may still occur after cochlear function returns to normal.Through brain functional imaging, it has been found that local cerebral blood flow in the temporal lobe auditory cortex of patients with tinnitus increases,and there is high metabolic activity.It is speculated that there may be abnormal cortical changes in the brain.He Jianbei et al.[5] supposed that this was due to the centralization of tinnitus.Recent studies have confirmed that tinnitus is rooted in the plasticity of the auditory center; that is, it originates from peripheral auditory system damage, which can cause abnormal excitement and even functional reorganization of the brain stem and cerebral cortex.

Potential mechanism of “central plasticity”in tinnitus

Tinnitus-related brain regions

Lan Jiahui et al.[6] found that the main parts of the tinnitus central system include the inferior colliculus,cochlear nucleus,auditory cortex,and limbic system.

The inferior colliculus is the key part of auditory signal transmission, and the γ-aminobutyric acid(GABA)receptor in the inferior colliculus can regulate the excitability or inhibition of neurotransmitters, thus regulating the balance between excitation and inhibition of the auditory pathway.The cochlear nucleus is composed of the dorsal and ventral nuclei,which consist of all cochlear afferent nerve fibers.At the end of the auditory projection system and the trigger point of the first synapse [7-8], central plasticity may occur in the dorsal and ventral nuclei of the cochlear nucleus.The auditory cortex can directly sense or regulate tinnitus;hence,it is an important area associated with tinnitus.

The limbic system is widely associated with other brain structures, and has gradually received extensive attention in tinnitus research.The limbic system completes cognition, memory, etc.by integrating the input signals of various sensory systems (such as pain,touch, temperature, taste, etc.), learning ability,emotional control, and other activities.After it is introduced into the limbic system, tinnitus will be judged as a bad signal by the limbic system, and concurrently activate the central memory system.Therefore,even if the cochlear function is restored,the central memory may still have tinnitus, and this"central plasticity" is a very difficult problem in treatment.The hippocampus is the key part of limbic system.It is also the main regulatory center of the hypothalamus-pituitary-adrenal axis.Studies like that of Liu Junxiu et al.[9] found that glucose and lactate levels in the hippocampal nuclei of rats with acute tinnitus were significantly higher than those of normal rats.This suggested that the activity of hippocampal neurons in patients with tinnitus was enhanced, further proving that the marginal system played an important role in the causes of tinnitus.

Plasticity changes of neuroelectrophysiology of the auditory system

Under normal circumstances, each neuron in the auditory pathway has spontaneous and random electrical activity, and external sounds are compiled into electrical signals in the ear, which are then perceived by the body.Concurrently, synchronous discharge activity occurs between nerve fibers;however, it is not transmitted as sound information.In individuals with a certain degree of hearing loss and other peripheral nerve input reduction, the central nervous system will be compensated.The central inhibitory effect on efferent nerves such as the cochlea is correspondingly reduced, and eventually tinnitus is caused by increased spontaneous discharge activity of the auditory cortex [10-11].Tinnitus caused by peripheral auditory system injury will be recognized as bad signal by the center.In order to adapt to the input of bad signal, the center produces abnormal activity of neuron synapse and spontaneous excessive abnormal discharge.Eventually,the excitability of neurons in the auditory cortex increases, synaptic ultrastructural changes, and functional reorganization causes tinnitus to exist in the center for a long time [12-13].Kaltenbach et al.[14] put forth that strong acoustic stimulation such as increased abnormal discharges,increased synchronous activity of nerves, and enhanced activity can also cause plasticity adjustment of central neurons.

Changes of central neurotransmitters

A neurotransmitter is the medium used to transmit information in the top-down regulatory system of the human body.After being synthesized in neurons, it is stored and released by nerve endings, and it needs to combine with specific receptors when it plays its role[15].Neurotransmitters have the functions of transmitting nerve signals and helping nerve cells to metabolize.The normal distribution of neurotransmitters and their receptors is an important prerequisite for the activity of nerve cells.Yang Songbai et al.[16] found that the central plasticity regulation of acupuncture on rats with tinnitus may be due to the change of neurotransmitter level.The main neurotransmitters in the auditory pathway are GABA,5-hydroxytryptamine(5-HT),glutamic acid,dopamine,etc.The abnormal release of these neurotransmitters or redistribution of their receptors will lead to an imbalance between the excitation and inhibition of auditory pathway, which is also an important cause of tinnitus [17].A GABAergic neuron is an inhibitory neurotransmitter in auditory cortex.Some studies have speculated that a decrease of GABA receptors may also be an important mechanism of tinnitus [18].The 5-HT nerve is an important regulatory network and can activate GABA [19].Its nerve endings widely exist in the auditory nucleus of the central system, so it can sense and regulate sound[12].

Psychological factors and central memory

The load degree of psychological factors is also an important factor for the occurrence and even aggravation of tinnitus, such as social pressure, low mood, anxiety, and depression.The arousal of psychological depression is an important reason for the persistence of tinnitus symptoms [20-21].In 1990,Jastreboff et al.proposed that if the bad signals of tinnitus spread to the limbic system through the autonomic nervous system, it will induce anxiety,panic, irritability, and other bad emotions [22].These bad emotions will be memorized by the central system,resulting in a vicious circle of bad emotions-tinnitus-bad emotions, leading to further aggravation of tinnitus.

Exploration of the possible mechanisms of acupuncture treatment in tinnitus at different levels

Changes of central neurotransmitters GABA and 5-HT

It has been mentioned that changes in central neurotransmitters are an important factor in tinnitus.Ding Lei et al.[23] included 40 patients with tinnitus for acupuncture treatment.The main points, which were selected according to syndrome differentiation,were from the points of Yifeng (SJ17), Tinggong(SI19), and Tinghui (GB2).The tail of the main point was connected with a G6805O-2A therapeutic instrument, and the waveform was a continuous wave,the frequency was 30 Hz, and the needle was kept for 15 min once a day, 14 times as a course of treatment.The levels of 5-HT and GABA in peripheral serum of patients before and after treatment were measured.Conclusion: after acupuncture, GABA content increased (P＜0.01) and 5-HT content decreased (P＜0.01).It is speculated that the changes of the central neurotransmitters 5-HT and GABA before and after treatment may be the mechanism of acupuncture treatment of tinnitus.

Discussion of the mechanism of acupuncture treatment in tinnitus based on functional magnetic resonance imaging technology and anatomy

Liu Xiangwei et al.[24] studied the mechanism of acupuncture treatment of nervous tinnitus based on functional magnetic resonance imaging technology.Eight eligible patients were included in the study.Before treatment, they underwent magnetic resonance imaging scanning for the collection of collect data.They were acupunctured at the main points, such as SI19, GB2, Shuaigu (GB8), SJ17, Ermigen (R3) (all affected sides), and Fengchi (GB20) and Zhongzhu(SJ3)(all bilateral sides).They were treated for 30 min every time, once every other day, 3 times a week, and 10 times a course of treatment.After one course of treatment, the patients underwent MRI scanning again.After treatment, the activities of the right superior temporal gyrus and the superior frontal gyrus were enhanced.Because the superior temporal gyrus belongs to the auditory pathway area, it is speculated that the mechanism of acupuncture in treating tinnitus may be that acupuncture weakens abnormal cochlear nerve electrical activity (tinnitus signal) and compensatory reorganization occurs in auditory cortex.Wei Yarui et al.[25] explored the abnormal dynamic functional connection of patients with chronic tinnitus based on resting functional magnetic resonance imaging technology and the related neural mechanism of acupuncture and moxibustion treatment of tinnitus.Seventeen patients with chronic tinnitus were included as the acupuncture treatment group and 22 normal persons as the control group.The main acupoints of acupuncture were SI19, GB2, SJ17, GB8 and R3 (all affected sides), and GB20 and SJ3 (both sides).Each treatment lasted 30 min, once every other day, 3 times a week, and one treatment course spanned 4 weeks.They found that acupuncture can reduce the dynamic functional connection of patients with chronic tinnitus and improve tinnitus.

In the treatment of tinnitus,Zhao Minghua et al.[26]often combined acupuncture with medicine, and according to the distribution of scalp functional areas,it selects the points of auditory fainting region Tinggong, Tinghui, Shuaigu, Qubin, etc., and applies the method of tonifying and purging after the arrival of qi, which has a remarkable effect.The auditory fainting region, proposed by Professor Jiao Shunfa, is mainly located in the middle of the superior temporal gyrus of the cerebral cortex, so the auditory pathway can be stimulated by deep needling and strong stimulation of the above acupoints.This accelerates the blood circulation around the ear and relaxes the ear muscles,thus reducing tinnitus and improving hearing.An anatomical study showed that the cochlear nerve shared four-level conduction pathways, and the third-level neurons crossed the sphenopalatine ganglion at the facial nerve.Therefore, the cochlear nerve and sphenopalatine ganglion cross indirectly through the facial nerve [27].Zhangxin et al.[28]found that tinnitus was reduced or even completely resolved during the clinical acupuncture of sphenopalatine ganglion for rhinitis in most patients.After acupuncture at the sphenopalatine ganglion,patients with idiopathic tinnitus were treated more than 1000 times,and certain results were achieved.

Therefore, it can be speculated that there are two mechanisms for acupuncture at the points around the head and ears to treat tinnitus.One is based on central plasticity; acupuncture changes the wrong central pattern of the cerebral cortex caused by tinnitus through strong stimulation, and makes the cerebral cortex adapt to internal and external environmental changes to produce benign functional reorganization.Second, the external stimulation of acupuncture can accelerate the contraction of muscle vessels around the ears, accelerate blood circulation and metabolism, and improve the blood supply of the auditory system, thus improving tinnitus.

The acupoint-nerve pathway

To sum up,combined with the research statistics,when acupuncture is used to treat tinnitus, the main points are concentrated in the ear periphery, and the high-frequency points include Ermen (TE21), SI19,GB2,SJ17,and GB8[29-31].

Stimulation signals are transmitted by the nervous system after acupuncture.The nerve mechanism of the Du Guoliang [32] needle stimulating the ear to treat tinnitus may be that it stimulates the sensory endings of the trigeminal nerve and activates the release of GABA receptors in the dorsal nucleus of lateral lemniscus or GABA receptor in the inferior colliculus,thus inhibiting the abnormal discharge of the inferior colliculus.Through the experiment of acupuncture at SJ17 and GB20 points in SD rats, retrograde tracing FG and observing Fos expression in the central nervous system, it was concluded that there are two pathways from sensory signals to the inferior colliculus after acupuncture at tinnitus acupoints.One is the acupoint stimulation point-trigeminal ganglion-SP5(inter-polar subnucleus of trigeminal spinal nucleus)-CI (inferior colliculus pathway).Another is acupoint stimulation point-trigeminal ganglion-SP5(inter-polar subnucleus of trigeminal spinal nucleus)-(nucleus of lateral lemniscus)-CI (inferior colliculus pathway),which provides a valuable basis for studying the neural mechanism of acupuncture treatment of tinnitus.

It can be speculated that acupuncture can improve or even cure tinnitus by stimulating the acupoint-nerve pathway around the ear, regulating unbalanced neurotransmitters,inhibiting abnormal nerve discharge,correcting wrong auditory pathway patterns and establishing new auditory pathway nerve conduction patterns.

Conclusion

Although acupuncture therapy belongs to traditional Chinese medicine, there is an inseparable close connection between Chinese and western medicine in various fields in the study of the mechanism of acupuncture treatment.At present, the research on the neural mechanism of acupuncture treatment of tinnitus is mostly based on animal models, lacking a large number of multi-level clinical data support.Different stimulation modes, such as acupuncture intensity,depth, frequency, time, and acupoint selection, will affect the transmission between the central nervous system, so it is difficult to evaluate the mechanism of acupuncture treatment [33].However, we still have to combine the theories of Chinese and western medicine and science and technology, explore the mechanism of acupuncture in the treatment of tinnitus at multiple levels, and define the treatment direction, finally improving the clinical efficacy.