Acupuncture, Neurobiology and the Nitric Oxide Connection

Integrative Medicine and Acupuncture

William R. Morris

Research into the physiological effect of acupuncture is emerging at a rapid rate. From Calcium mediated signal transduction in meridian system and acupuncture where the pattern of magnetic field on the human scalp is mapped by SQUID (Superconducting Quantum Interference Device) showing that the Governor Vessel is a major pathway of magnetic flux on the scalp(14), to the gate-control theory put forth by Wall and Melzack in 1965 (8)(5) to functional MRI work mapping the brain body connection where a point needled in the toe causes the visual cortex to ‘light up.’

 Nitric oxide (NO) Functions

Nitric oxide research seems to show that acupuncture modulates nitric oxide activity in the brainstem somatic sensory paths (nucleus gracilis), basal ganglia striatum, and the cerebral cortex, as well as the hippocampus. Nitric oxide is a messenger molecule with biological actions that range from signal transduction to cell killing. Nitric oxide accounts for tonic relaxation of all types of blood vessels and non-adrenergic and non-cholinergic relaxation of the gastrointestinal tract. Nitric oxide acts as a neurotransmitter in the central and peripheral nervous system, contributes to the antimicrobial activity of macrophages, decreases platelet aggregation, and is involved in hormone release.

Current evidence indicates that, in the CNS, nitric oxide is produced enzymatically in postsynaptic structures in response to activation of excitatory amino acid receptors. It then diffuses out to act on neighboring cellular elements, probably presynaptic nerve endings and astrocyte processes. In several peripheral nerves, and quite possibly in parts of the CNS as well, nitric oxide might be formed presynaptically and thus act as a neurotransmitter(2).

Although the influence of NO on striatal neuronal activity remains to be thoroughly characterized, evidence has accumulatedsuggesting that NO signaling may mediate and/or regulate multipleaspects of striatal neurotransmission including the integration of convergent motor information within striatalnetworks. A major component of the cortical regulation of the nigrostriatal dopamine (DA) system is known to occur via activation ofstriatal efferent systems projecting to the substantia nigra through the intermediary role of striatal nitric oxide synthase(NOS). Striatal NOtone regulates the basal activity and responsiveness of DA neuronsto cortical and striatal inputs. In additionstriatal NO signaling may play an important role in the integrationof information transmitted to basal ganglia output centers viacorticostriatal and striatal efferentpathways(15).

 Acupuncture modulates NO concentration

Increased concentrations of NO were found on the skin adjacent to meridians and acupoints relative to surrounding areas. The hypotensiveand bradycardiac responses to EA ST36 are modified by influencesof L-arginine-derived NO synthesis in the gracile nucleus. It appears that NO plays an important role in mediating thecardiovascular responses to electro-acupuncture ST36 through the gracile nucleus(1).

The work of Dr. Sheng-Xing Ma at the Harbor-UCLA Medical Center suggests that at least some acupuncture effects involve transmission of biological information by nitric oxide.(7) In addition, enhanced NO in the acupoints/meridians is generated from multiple resources including neuronal NOergic system, and NO might be associated with acupoint/meridian functions including low electric resistance. He recently reported that stimulation of hindlimb acupounts (LB 64, 65) resulted in increased synthesis of the signaling molecule nitric oxide at a specific location of the brain stem of rats.

Other studies demonstrate the activity of nitric oxide modulation through acupuncture, needling Zusanli (ST 36) may modulate NOS activity in the hippocampus under diabetic conditions(3). In addition, Li et al investigated 42 people between the ages of age 55 and 70 were given the warm needling at Zusanli (ST 36), the results showed that IL-2 and NO contents increased significantly after the warm needling (P < 0.01)(6).

Hippocampal Function Related to Nitric Oxide Synthase (NOS)

The hippocampus is a central processing area at which meet the sensory and associative cortex, Learning and memory are essential to an animal’s ability to survive and thrive. In many species, including humans, a cortical structure known as the hippocampus is critical for the formation of long-term memory. Studies of long-term potentiation (LTP) in the hippocampus help to show how memories may be encoded and stored at the synaptic level. suggested that acupuncture treatment may modulate NOS activity in the hippocampus under diabetic conditions(3, 9). In addition, Kang et al showed that acupuncture modulates the expressions of NOS and c-Fos in the gerbil hippocampus post transient global ischemia(4).

The hippocampus matures postnatally, which means that the functions it serves are not available for some time after birth. According to Nadel, the role of the hippocampus is the core of a “spatial/cognitive mapping system.” and involves possible relations between space and language(11). In infant rats, stressful experiences can impact postnatal hippocampal development as well as the later development of the hippocampus in relation to unusual “fears and phobias”. It is generally assumed that in the adult organism the hippocampus interacts with the neocortex during memory “consolidation” so as to enable information to be permanently stored in cortical sites(10-13).

Since the hippocampus has connections with the hypothalamus and other structures dealing with somatovisceral, emotional, and endocrine functions where different parts of the brain combine to form a cognitive map, we can then understand the possibility of actual changes in all these areas, including the consolidation of pain memories.

 In Closing

The neurobiological connection is a promising area for the development of a deeper understanding about how acupuncture works. The changes that have been demonstrated in the hippocampal nitric oxide content in relation to acupuncture stimulation may present a fertile ground for the investigation of the psychosocial impact of acupuncture interventions. AS a speculation, it would seem to the author that memories in post traumatic stress syndrome that cause flashbacks of traumatic events could be modulated though acupuncture interventions.


1.         Chen S, Ma S-X. 2003. Nitric Oxide in the Gracile Nucleus Mediates Depressor Response to Acupuncture (ST36). J Neurophysiol 90: 780-5

2.         Garthwaite, Department of Physiology UoL, UK. 1991. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 14: 60-7.

3.         Jang MH SM, Lim BV, Kim HB, Kim YP, Kim EH, Kim H, Shin MS, Kim SS, Kim CJ., Department of Physiology CoM, Kyung Hee University, Dongdaemoon-gu, Seoul, Korea. 2003. Acupuncture increases nitric oxide synthase expression in hippocampus of streptozotocin-induced diabetic rats. Am J Chin Med. 31: 305-13

4.         Kang J-E, Department of Acupuncture and Meridianology GSoE-WMS, Kyung Hee University, Yongin, Korea, Lee H-J, Department of Acupuncture and Meridianology GSoE-WMS, Kyung Hee University, Yongin, Korea, Lim S, et al. 2003. Acupuncture Modulates Expressions of Nitric Oxide Synthase and c-Fos in Hippocampus After Transient Global Ischemia in Gerbils. The American Journal of Chinese Medicine Vol. 31: 581-90

5.         Lewith G K, JN. 1984. Physiological and psychological explanations for the mechanism of acupuncture as a treatment for chronic pain. Soc Sci Med 19: 1367-78

6.         Li SJ, Tang J, Han JS. 1982. [Tolerance to 5-HT and its implication in electro-acupuncture tolerance and morphine tolerance]. Zhongguo Yao Li Xue Bao 3: 159-63

7.         Ma SX. 2003. Enhanced nitric oxide concentrations and expression of nitric oxide synthase in acupuncture points/meridians. J. Alt. Complement. Med. 9: 207-15

8.         Melzack R WP. 1965. Pain mechanism: a new theory. 150: 971-9

9.         Mi-Hyeon Jang M-CS, Baek-Vin Lim, Hyun-Bae Kim, Young-Pyo Kim, Ee-Hwa Kim, Hong Kim, Mal-Soon Shin, Sung-Soo Kim, Chang-Ju Kim. 2002. Acupuncture increases nitric oxide synthase expression in hippocampus of streptozotocin-induced diabetic rats. American Journal of Chinese Medicine

10.       Nadel L. 1994. Multiple memory systems: What and Why. In Memory Systems, ed. DSaE Tulving, pp. pp. 39-63. Cambridge, MA: MIT Press

11.       Nadel L. 1995. The psychobiology of spatial behavior: The hippocampal formation and spatial mapping. In Behavioural brain research in naturalistic and semi-naturalistic settings: Possibilities and Perspectives, ed. H-PL E. Alleva, L. Nadel, A. Fasolo and L. Ricceri: Kluwer Press

12.       Nadel LaJ, W.J. The role of the hippocampus in PTSD, panic and phobia. In Hippocampus: Functions and Clinical Relevance, ed. N Kato. Amsterdam: Elsevier Science B.V.

13.       O’Keefe JaN, L. 1978. The hippocampus as a cognitive map: Oxford: The Clarendon Press.

14.       Shang C. The Meridian System And The Mechanism Of Acupuncture.

15.       West AR, Grace AA. 2000. Striatal Nitric Oxide Signaling Regulates the Neuronal Activity of Midbrain Dopamine Neurons In Vivo. J Neurophysiol 83: 1796-808



Monoculture Culture of the Mind, a Way Out:

 Knowledge Building through Cases


The case as tool for knowledge development sustains primacy if considered as a longitudinal series of data. In Monocultures of the Mind, I established history and advantages of the case in what might be called ‘local knowledge’ – that is, direct clinical experience of master practitioners. Here, the discussion on cases continues!

The field has resources for managing and developing cases. The editors of the journal Global Advances in Health and Medicine have provided, under “For Authors,” a template that can be downloaded for case presentation. This template has been vetted across various portions of the healthcare community and can serve as a starting point for case reporting in all master and doctoral programs within the field.

In this article, the matter of case Based Learning is addressed. When I attended a master’s degree program in medical education at USC, we interviewed Luann Wilkerson who initiated Harvards New Horizons program – one of the first case based approaches to medical education. This set the stage for me.

Case-Based Learning

Case-based learning (CBL) is an approach that challenges learners to learn through engagement in real problems. Adult learners expect a foundation of critical thought and context. This expectation is that learners build their knowledge by combining previous knowledge with current knowledge 1. The teacher serves in the role of facilitator.

Contrary to an expert speaking each piece of information, the case study provides the learner a context for developing problem-solving skills. Further, small group case-based learning encourages collaboration and cultural competencies now expected by members of society for practitioners of medical disciplines 4,5.

A time-honored tradition in Chinese medicine, case-based teaching offers a tool for conveying expert knowledge in service to medical education. Case studies make available the insight, thoughts and methods of expert practitioners by capturing their views on practical applications and theoretical framework. This form of knowledge provides a foundation for the transmission from generation to generation in literary form.

At each level of learning, case narratives provide physicians with tools to communicate their knowledge about patients, their medical problems and the interventions. More than storage-retrieval devices, formative discourse of the case shapes the reflections, thoughts, talk and actions of learners and their teachers. Further, reform of the medical record is central to the improvement of medical education, patient care and clinical research 6.


One type of case-based teaching, called ‘problem-based learning’ (PBL), reveals information in stages and at critical moments in the development of the case. The problem-based learning model requires extensive faculty and economic resources in comparison to the more minimal case-based learning presentation model. There are several distinct features that define the PBL approach 7:


  • Real tasks, issues, and problems provide a context for the learning experience.
  • PBL learning is an ‘emergent’ learning process as faculty and learners are involved in a participatory and co-operative model for learning, planning, production, and evaluation while designing, implementing, and refining the curricula.
  • The PBL approach is grounded in academic research on learning 8.
  • PBL can be used to demonstrate competencies relative to life-long learning since it can be used to stimulate learners to take responsibility for their own learning. The faculty members typically facilitate and there are few lectures and less structure of content.
  • PBL also provides a tool for collaborative care competencies among learners, stresses the development of problem solving skills within the context of professional practice, promotes effective reasoning and self-directed learning, and is aimed at increasing motivation for life-long learning.


Case-based and problem-based learning methods are not without detractors. There are studies showing that active problem solving for junior learners is less effective than studying examples that experts have already solved 9,10. Active problem solving tends to be better suited to senior learners who have memorized the vocabularies of practice. Thus, the case vignette is often more suited to early learners while active problem solving is more relevant in later portions of a program. Many of the PBL strengths are shared in case-based learning.


Case presentation can be used throughout a range of teaching methods; for example, case vignettes can be used during a lecture to highlight experience. Cases also provide seeds for rich critical thought-based dialogues within small groups. The dynamics can be shifted so that the learner presents the case. The latter method can be used to demonstrate summative assessment of competencies at important milestones within a program.


“Cases stimulate the imagination, open up possibilities, provoke us, and perhaps disturb us. They fill in the gaps left by powerful generalizations, reminding us that every illness is unique in the same way,” opines Ian R. McWhinney who believes case studies have played an important part in the annals of Western medical practice—as can be seem in Edward Jenner’s case reports on his discovery of the small pox vaccination 12.


Case Study as Program Evaluation Tool

Portfolios are increasing as a valuable evaluation tool for medical education. The Accreditation Council for Graduate Medical Education (ACGME) supports the development of the portfolio as a “web-based professional development tool for residents to record, organize, reflect on, and seek feedback on their learning experiences.” The expectation is that the methods will become an integral portion of the next accreditation cycle for ACGME 13.

Cases are commonly used artifacts in the portfolio presentation. There are several reasons for this. The case is an excellent tool for summative evaluation of program level competencies. This is partly due to the ability of program leaders to use the case to assess competencies across the curriculum. The well-constructed case may be suitable for publication and can be used for promoting the professional development of the learner. Such works in publication reflect well upon the program.


Cases provide access to knowledge that is connected to its origins. Exploring cases highlights the thought of significant physicians throughout the literate history of Chinese medicine. The value of local knowledge over general knowledge is realized through the case, in particular the essence of expertise.




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