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J Chiropr Educ. 2010 Fall; 24(2): 187–193.
PMCID: PMC2967343

Utilizing Molecular Details of the Pain System to Illustrate Biochemical Principles

Abstract

To capture student interest and show clinical relevance, molecular details from the pain system can be used as supplemental examples to basic biochemistry lectures. Lecture topics include glutamate, substance P, calmodulin-dependent protein kinase II, synaptic proteases, calcitonin gene-related peptide, and neuronal protein synthesis. These topics are utilized to illustrate basic biochemical issues and are linked to pain-related topics such as pain transmission, synaptic plasticity, long-term potentiation, and central sensitization. For analysis, a brief survey was administered to evaluate student attitudes toward a representative lecture segment. Survey results support the premise that utilizing the pain system is an effective tool to engage chiropractic students during basic biochemistry lectures.

Key Indexing Terms: Biochemistry, Chiropractic, Education, Neuronal Plasticity, Pain

Introduction

Teaching biochemistry in any setting is challenging. As part of the onslaught of 1st-year basic science instruction at a chiropractic college, teaching biochemistry becomes a truly difficult endeavor. Typically, the various anatomical science courses are the focus of beginning chiropractic students, so the biochemistry instructor must resort to any and all strategies to catch the students' attention. One approach to engage students in any basic science course is to utilize clinical correlations.1–5 This works well in biochemistry, to an extent; some good examples are bilirubin, alkaline phosphatase, and serum lipids, among others. There are, however, limitations and trade-offs with this approach (ie, many clinically relevant examples are obscure and patients with these conditions are less likely to present in a chiropractor's office).

A clinical complaint guaranteed to be encountered in any chiropractic practice is pain. With recent advances in understanding the pain system at the cellular and molecular levels,6–9 pain represents a terrific instructional tool to illustrate basic biochemical concepts. Biochemistry at the University of Western States (UWS) is taught as a two-quarter sequence. The first course covers fundamentals with the focus on amino acid and protein structures, enzymes, and nucleic acids (including transcription and translation). The second course deals with intermediary metabolism and the roles of vitamins. Students are typically more engaged in the topics covered in metabolism and vitamins due to inherent nutritional connections, so molecular details from the pain system are primarily utilized to accent the more basic biochemical concepts in the first biochemistry class. What follows is an example utilizing glutamate that illustrates a method for introducing pain topics into basic biochemistry lectures. Additionally, other pain-related topics are provided with accompanying background references. Results are presented from a brief survey of student attitudes toward this lecture approach.

Methods

Lecture Topics

A list of pain-related topics utilized in the introductory biochemistry course taught at UWS is displayed in Table Table1.1. The sequence of topics in the table follows that of pain-related presentations in the UWS biochemistry course. This lecture approach involves augmenting basic biochemical concepts with brief lecture segments, typically lasting 15 minutes, which utilize the cellular and molecular events during pain transmission. The primary focus is on events or activities associated with wide dynamic range (WDR) neurons, the primary pain transmission cell in the dorsal horn of the spinal cord. As a means to illustrate this approach, a lecture segment involving glutamate and its role in pain signaling is presented below. Additional pain-related topics utilized throughout the biochemistry course are described briefly.

Table 1
Potential biochemical topics to be correlated to the pain system

Glutamate is the primary excitatory neurotransmitter in the central nervous system (CNS) and plays a critical role in transmitting sensory input derived from noxious stimuli.10, 11 To set the stage for this discussion of glutamate, as well as other pain topics, a brief depiction of a classic pain study12 is presented at the beginning of the lecture segment (ie, the “rodent paw-clamp model”). In the experimental model described, a rodent is subjected to acute, repetitive noxious stimuli by the attachment of a clamp to the animal's paw. Whether using chemical algogens (eg, capsaicin) or mechanical noxious insult to an animal, this type of experimental approach6 has led to much of the understanding of the cellular and molecular events in neurons responding to acute noxious stimuli.6–9 The rodent paw-clamp model gives the student a simple (but memorable) visual model of the pain system and it is referred to throughout the term. The rodent paw-clamp model is only described during the lecture segment; however, as a symbolic act of sympathy for the animal and as a means to grab the students' attention, this portion of the lecture is given while a large paper clamp is affixed to several digits of the lecturer's hand. Warning!!! During the course of the discussion the clamp can become quite uncomfortable. The rodent paw-clamp experimental pain model conveniently leads to discussion of glutamate release from afferent nociceptors, WDR neurons in the dorsal horn, glutamate receptors [N-methyl-D-aspartate receptors (NMDA-Rs)10 and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPA-Rs)10, 13], synaptic plasticity9, 14–16, long-term potentiation (LTP),17–21 and central sensitization.7, 20, 22, 23 These descriptions are brief (due to the presence of the paper clamp and its progressive impact on the lecturer's focus) and rudimentary (as these students are in the first term at UWS). Most important, the students are warned that the term central sensitization is becoming widely employed and its exact meaning may depend on the user and context.22 The International Association for the Study of Pain (IASP) uses the definition, “an enhanced responsiveness of nociceptive neurons in the CNS to their normal afferent input.” Other references to central sensitization may imply a heightened awareness of pain perception without clarifying where or how the pain is generated.22 The idea of plasticity and, more specifically, synaptic plasticity is further discussed and its historical context is stressed.20

Other pain-related topics (Table (Table1)1) that lend themselves to basic biochemistry lecture examples include substance P,24–27 calmodulin-dependent protein kinase II (CaMKII),19 synaptic proteases,28, 29 calcitonin gene-related peptide (CGRP),30–35, c-fos/ Fos,6, 12, 36–40 and neuronal protein synthesis.41–43 For example, the 11 amino acid peptide substance P is co-released with glutamate and its role in nociception is emphasized. CaMKII is discussed as a specific example of a kinase whose involvement in neuronal plasticity is pivotal. Synaptic proteases are presented as a special subset of the large family of proteases which, among their many actions, degrade peptide neurotransmitters. CGRP and calcitonin demonstrate an excellent example of alternative RNA splicing. Both these peptides are physiologically important and CGRP is linked to substance P and nociception. Activation of c-fos, an immediate early gene, is discussed as one of the early events in WDR neurons during pain transmission. Its protein product, Fos, acts as a transcription factor and serves as a dramatic example of regulating protein synthesis at the transcriptional level. Finally, localized dendritic protein synthesis is contrasted to axonal protein synthesis and discussed in the context of neuronal plasticity.

Analysis

As a measure of students' reactions to this lecture approach, a brief questionnaire (see Appendix) was administered to a large student group (n = 89) who took biochemistry at UWS in fall 2008. The survey focused on the lecture segment involving the amino acid glutamate and its role in pain transmission in the dorsal horn. This glutamate segment was selected because it introduced the overall approach of using pain topics in the biochemistry lectures and described an experimental model to be used in this and subsequent pain-related segments of the course. The questionnaire was approved by the UWS Institutional Review Board as an expedited review. The survey was administered 6 months after the students had received the glutamate lecture and was given in a classroom setting to encourage a high return rate. Students participated anonymously and were blinded to the potential use of the questionnaire results. The survey was independently collected and tallied. Student responses were based on a 5-point scale.

Results

The outcomes from the student survey are presented in Table Table2.2. The overall positive responses support the basic premise that utilizing the pain system is an effective method to engage chiropractic students during basic biochemistry lectures. The positive responses support both the use of an experimental pain model in the presentation and attempts by the instructor to do something illustrative (ie, paper clamp attached to lecturer's digits during the lecture). The response rate for the 6-month sampling group was 94% and demonstrates that the survey method provided representative sampling.

Table 2
Results from fall 2008 presentation

Discussion

This paper describes an instructional approach for teaching basic biochemistry that correlates well with chiropractic training. In addition to making biochemical instruction more pertinent for chiropractic students, this approach provides early exposure to the dynamic nature of the nervous system and fundamental issues regarding the processing of noxious stimuli. However, there are pitfalls with this lecture approach. Adding auxiliary topics to an already packed course schedule may be problematic. Also, there is the possibility that first-quarter chiropractic students may be overwhelmed by this advanced subject material. For both these reasons, the discussion of the pain system in these lecture segments is very basic and no attempt is made to cover pain transmission exhaustively. Only the basic molecules and general events are stressed. Concepts such as neuronal plasticity, long-term potentiation, and central sensitization are only introduced and left to be addressed more thoroughly in subsequent courses.

The rodent paw-clamp model is used repeatedly in pain-related lecture segments throughout the course. Repeated use of the same memorable experimental model expedites the delivery of information and minimizes the impact on coverage of other course topics.

The student survey was designed to elicit feedback on the general impression of the first pain-related lecture segment involving the amino acid glutamate. While the results were positive, they only provide qualitative feedback regarding student impressions. No attempt was made in this study to assess the quantitative impact (ie, student retention of the specific content discussed in the glutamate lecture). Also, feedback on additional lecture segments was not surveyed, so it is uncertain whether subsequent topics would produce equally favorable survey results. The questionnaire did address key issues pertinent to this lecture approach, and timing the survey at 6 months postlecture provides evidence that this lecture segment and overall instructional method were memorable and captured student interest. Given the volume and intensity of basic science coursework in 1st-year chiropractic programs, this is a significant outcome.

A reasonable critique of the student questionnaire is the use of descriptive prompts in the survey introduction. Given the 6-month interim between the lecture segment and the analysis as well as the brevity of the glutamate segment (20 minutes) nested within the numerous 1st-year basic science lectures, the authors felt it was reasonable to remind the students of the lecture segment without influencing their qualitative responses.

This questionnaire was created without pilot testing and no attempt has been made toward validity testing of the questionnaire results. In any follow-up survey, recall bias can be a factor and its impact on responses can be difficult to predict.44 Relatedly, the overall success of the students in the biochemistry course may also factor into the survey responses and represent another internal validity issue.

By their very nature, these pain-related topics link biochemistry lectures with other classes in the chiropractic program. The instructor frequently reminds students of related issues covered concurrently in cell biology and suggests how a subsequent neurophysiology course will elaborate on a given topic.

The accompanying references (Table (Table1)1) were selected on the basis of providing background material for an instructor (without extensive training in the neurosciences) interested in incorporating pain-related topics in a basic science course. No attempt was made to catalog an exhaustive list of primary articles; however, those can be found in a number of the reviews cited below. The references include a limited number of primary sources where historical relevance was considered critical, numerous review articles because the authors believed that those would be the most useful tools for the reader, and a few tertiary sources when more background information was deemed useful.

Conclusion

Various examples of links between basic biochemical issues and pain topics are provided. Student survey results demonstrate that utilizing pain-related topics to augment fundamental biochemical concepts can be an effective instructional method in a chiropractic degree program. Pertinent references are cited as tools for those instructors interested in adopting these auxiliary topics into a basic biochemistry course.

Funding Sources and Conflicts of Interest

There are no funding sources or conflicts of interest to declare.

Appendix: Educational Research Questionnaire
Biochemistry Can Be Painful

During the fall 2008 quarter, coursework in Biochemistry I included a description of the role of glutamate as a neurotransmitter. The topic was discussed during an early lecture on amino acids and utilized nociception, molecular details of the pain system, an experimental model (rodent with clamp attached to paw), instructor simulation of the experimental model (ie, paper clamp attached to instructor's fingers), and brief discussion of related topics (ie, neuronal plasticity, central sensitization). This was one of several segments throughout Biochemistry I linking basic biochemistry to the molecular details of the pain system.

Prior to this lecture, were you aware that the amino acid glutamate was a neurotransmitter?

YES _______ NO _______

For the following questions rate your response to the statements provided (Circle the most appropriate description.)

In general, illustrating basic science concepts by utilizing practical and clinical applications is something I appreciate.

AgreeSlightly AgreeNeutralSlightly DisagreeDisagree

This lecture segment describing glutamate as a neurotransmitter in the pain system effectively caught my attention.

AgreeSlightly AgreeNeutralSlightly DisagreeDisagree

The topic of pain was an important factor in capturing my interest regarding glutamate.

AgreeSlightly AgreeNeutralSlightly DisagreeDisagree

The use of a simple experimental model (rodent with paw clamp) was a useful tool to give context to glutamate's role as a neurotransmitter.

AgreeSlightly AgreeNeutralSlightly DisagreeDisagree

Attaching a paper clamp to the instructor's fingers (simulating the experimental model) was useful in making the presentation memorable.

AgreeSlightly AgreeNeutralSlightly DisagreeDisagree

Contributor Information

Robert Boal, University of Western States.

Richard G. Gillette, University of Western States.

William H. Borman, University of Western States.

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Articles from The Journal of Chiropractic Education are provided here courtesy of Association of Chiropractic Colleges