Neural pathways and pain sensations

One of your lower right premolar teeth has to be drilled and filled. It shouldn’t take too long says your dentist. You decide to undergo the procedure without having your gum injected with lidocaine but within a few seconds of drilling the pain has become too intense. The dentist gives you the injection, and after a few minutes, continues with the procedure. The tooth turns out to be beyond repair and, with a lot of tugging it is extracted. That’s going to be sore for a few days says your dentist, I suggest you get some ibuprofen.

The neural pathway and the nerve fibre types which convey the sensations during the first few seconds of the dental procedure and in the few days afterwards; and the mechanism of action in this situation of lidocaine and ibuprofen:

The dental procedure that was carried out was most probably due to cavities in the tooth. If the cavity was deep enough (deep enough to touch the nerve) this could have caused the patient pain in itself. The removal of the decayed area by drilling and the filling of this area would have served to strengthen the tooth. However, the dentist decided that the tooth was beyond repair and eventually made the decision to extract the tooth. All of these procedures would have caused the nerves or pulp to become temporarily inflamed and damaged which would have lead to the activation of certain cells and fibres of  both the immune system and central nervous system to elicit a pain perception to the patient and trigger an inflammatory response.

The sensory nerves of the teeth (and the face) are called the trigeminal nerves (analogous to dorsal root ganglia of spinal cord). There are one of these nerves on each side of the pons;. since the tooth that was drilled was one of the lower right teeth, it would be the mandibular nerve that would have been the sensory neuron and relayed the pain sensations that arose from the drilling. The nerve fibres would have been stimulated and the signal would travel along these nerves to the ganglion and onto the spinal trigeminal tract where they synapse. Here, second order neurons would travel to the ventral trigeminothalamic tract and then synapse in the ventral posteriomedial nucleus of the thalamus. third order neurons would then travel to the facial region of the somatosensory cortex (in the cerebrum) where the information would be processed (trigeminal system goes down, crosses the brainstem then up to the cortex). These trigeminal nerves can be described as nociceptors, found in the dental pulp (endodontium) of the tooth (the cell body of these sensory neuron types are found in the trigeminal ganglia). Noticeptors are ‘ free nerve endings that terminate just below the skin in body organs'(http://www.mdbiosciences.com/Portals/42723/docs/Nociception-Neuropathic-Inflammatory%20Pain.pdf)(http://en.wikipedia.org/wiki/Trigeminal_nerve).

 

 

‘Pain perception is regulated by a balance of activity in nociceptive and non-nociceptive afferent fibres’ (Kandel, et al. 2012). There are two nociceptor types that are associated with pain (somatic) arousal. These are the A-delta and C-type afferent fibres. They are found throughout the body and act by sending the pain signals to the spinal cord which is then relayed to the brain. A- delta nociceptive afferents are responsible for rapid, sharp felt pain due to their higher conduction velocity (i.e. the pain initially felt by the patient a few seconds into the dental procedure) whereas the c-fibres are responsible for mediating the second longer lasting dull throbbing pain (which would have been felt by the patient in the days following the dental procedure due to the nerve damage caused by the tooth extraction). For these  C – type nociceptive fibres,  the pain sensation would have been carried by slower conducted unmyelinated nerve fibres which would mediate the slow pain (inflammation and  nerve damage) by the release of inflammatory mediators from the inflamed tissue, as opposed to the fast conducting myleinated fibres of the A delta afferents. The myleination/the mylein sheath factor of the A- delta fibres serves to increase membrane resistance and decrease capacitance, hence making the action potential conduction by electronic conduction faster. The myleinated axon consists of gaps called Nodes of Ranvier, which is where the ion channels are found. At these gap junctions of the axon, membrane resistance is low in comparison to the internode, allowing the action potential to be regenerated and jump/propagate to the next node by electrotonic conduction, hence the spread of currents between nodes is rapid and there is a fast transmission of the signal, thus a fast onset of pain.

(http://www.neuroanatomy.wisc.edu/SClinic/Weakness/Weakness.htm)Figure 1: Myelinated nerve fibre

 

 

 

The fact that the A- delta fibre is myleinated and the C- fibre is unmyleinated is what causes the two phases of pain (fast onset of intense pain and the slightly less intense but longer lasting dull throbbing ach).The A-delta and C-type fibres are also found in the mouth, although ‘due to the short distance between the mouth and the brain the two sensations might not be as clearly separated'(Narhi.M, et al, 1992).

 

Following tissue damage or inflammation during the dental procedure, this would activate the pain fibre nociceptor. The dental damage would cause the release of inflammatory mediators, which may include: Prostaglandins (PGE2, PGL2), Bradykinin, 5-HT, Histamine, Serotonin, Purines (ATP) among others. These mediators would exert their actions at different times, but all ultimately leading to sensitisation of the nerve ending response, called primary hyperalgesia. Prostaglandins are especially important mediators in pain response but have to be synthesised. During this prostaglandin synthesis pathway, tissue damage (e.g. caused by the tooth extraction) would cause membrane phospholipids to be converted to Arachidonic acid by the calcium dependent cPLA2 enzyme. This acid is then converted into PGG2/PGH2 (by the constitutive Cox-1 or the inducible Cox-2 enzymes). However these are unstable intermediates and so need to be converted into the biologically active prostaglandins, of which there are four types; PGI2 and PGE2 being the most important in pain response. PGI2 is able to directly excite nociceptors whereas PGE2 sensitises nerve endings to both thermal and mechanical stimuli (can also enhance the response of nerve endings to other stimuli to produce sensitization). These mediators may be released by mast cells or most likely by the white blood cells that would have been sent to the inflamed region as part of the inflammatory/immune response. These would then bind receptors on the sensory nerve endings (the ending would be sensitised), such as precursors for bradykinin, which would in turn, activate the signalling pathways of the transducers (thermal or mechanical sensitivity – not much is known about the mechanical pathway). This would then generate an action potential at the nociceptive terminal (which depending on whether the fibre is the myleinated A-delta or the unmyleinated c-fibre, would be propagated along the axons in different ways – as described previously). This would then lead to the release of neurotransmitters at the nerve ending. These axons would then send the impulses/pain signals with other incoming axons that would form a synapse with other neurons that project up to the brain. These neurons than synapse with the neurons in the thalamus region of the brain (part of the midbrain – magenta circle). The thalamus serves to organise the information (that was originally relayed and sent by the sensory neurons of the drilled tooth); once organised, the information is then sent to the sensory cortex. Here, the information/signal is interpreted as pain, which is then directed to the motor cortex and then back to the thalamus. The now interpreted pain signal is again organised and sends the signal and directs motor neurons back to the drilled tooth so that it can react to the pain (in this case the reaction would be the patient asking the dentist to stop the procedure after a few seconds and inject a numbing agent). (http://www.drugabuse.gov/publications/teaching-packets/neurobiology-drug-addiction/section-i-introduction-to-brain/4-pathway-sensation-pain-reaction-t). This is the pathway that ultimately causes the perception of pain.

 

After a few seconds of the dental procedure and due to the intense pain, the patient requested an anaesthetic. The dentist injected the local numbing agent into the gums surrounding the tooth, lidocaine (Lidocaine is the most common anaesthetic now used by dentists, due to the fact that it is Nitrogen and not Carbon based; the previously commonly used anaesthetic was novocaine which was carbon based which increased the risk of allergic reactions).

 

Lidocaine would have been used during the dental procedure as a local anaesthetic, but due to its relatively short half life of about 2 hours, Ibuprofen would have been used post-procedure as a pain killer. The drilling and filling and eventual tooth extraction procedures would have caused  the nerves/dental pulp to become temporarily inflamed, which is what ultimately caused the aching sensation felt by the patient and pain and sensitivity in the area, so in this case ibuprofen could also be described as an anti-inflammatory agent to give the patient pain relief. Ibuprofen is a non steroidal anti inflammatory drug and functions by inhibiting the Cox-1 and Cox-2 enzymes in the prostaglandin synthesis pathway (previously described). This means that Arachidonic acid wouldn’t be converted into the unstable intermediates PGG2/PGH2 and these would therefore not be converted into the biologically active prostaglandins; so ibuprofen serves to prevent prostaglandin production which ultimately prevents hyperalgesia. This is why Ibuprofen was the best choice for use as a pain killing/anti-inflammatory drug post-procedure, as opposed to paracetamol for example, which is a weak inhibitor of Cox enzymes. ‘Lidocaine on the other hand, functions by altering the signal conduction in neurons by blocking the fast  voltage gated sodium channel in the neuronal cell membrane that are responsible for signal propagation.'(Carterall,W. 2001). Due to this blockage, the postsynaptic neuronal membrane would fail to depolarize and therefore wouldn’t transmit an action potential. This is the local anaesthetic effect that arises; stops pain signals from being propagated to the brain but also stop these signals before they begin., thus stopping the patient feeling further pain during the dental procedure.  ( http://en.wikipedia.org/wiki/Lidocaine#cite_ref-novartis_29-0).

 

References

 

  • http://www.mdbiosciences.com/Portals/42723/docs/Nociception-Neuropathic-Inflammatory%20Pain.pdf.
  • (http://en.wikipedia.org/wiki/Trigeminal_nerve).
  • Kandel, E.R, et al.2012. Principles of Neuroscience, 5th edition. Chapter 24, pg. 545. New York; McGrave – Hill Medical
  • Narhi. M, et al, Role of intradental A and C-type nerve fibres in dental pain mechanisms. http://www.ncbi.nlm.nih.gov/pubmed/1508908.
  • http://www.drugabuse.gov/publications/teaching-packets/neurobiology-drug-addiction/section-i-introduction-to-brain/4-pathway-sensation-pain-reaction-t).
  • Carterall, William A. 2001. Molecular Mechanisms of Gating and Drug Block of Sodium Channel. Sodium Channels and Neuronal Hyperexcitability. Novartis Foundation Symposia 241. p. 206
  • http://en.wikipedia.org/wiki/Lidocaine#cite_ref-novartis_29-0.
  • Figure 1: http://www.neuroanatomy.wisc.edu/SClinic/Weakness/Weakness.htm.
  • Featured image: http://www.uic.edu/las/LIN/

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