Block 6: the senses Flashcards
Describe the role and anatomy of the olfactory nerve.
The olfactory nerve is a special sensory nerve which conveys sense of smell. It is formed of the bilateral olfactory bulbs and tracts. The olfactory bulbs rests on the ethmoid bone which has small openings (known as cribriform plate foramina). Nerves which form the respiratory mucosa project through these foramina from the upper nasal cavity to the olfactory bulb. The dura keeps these nerves in place. There are two pathways by which information can be carried from the olfactory bulb- the medial and lateral olfactory tracts. The medial olfactory tract projects to the primitive brain regions, such as limbic structures (responsible for emotional aspects of olfaction). The lateral olfactory tract projects to the piriform cortex, amygdala, and entorhinal cortex. These are collectively known as olfactory cortices. These pathways can, in turn, project to the prefrontal cortex and hippocampus.
Describe the functional anatomy and the nervous supply to the parotid, submandibular, and sublingual glands.
There are 3 major bilateral salivary glands- the parotid, submandibular, and sublingual glands. The parotid is the largest, and sits lateral to the mandible (just in front and slightly below the ears- ‘prearicular area’); the submandibular sits just below the mandible; and the sublingual gland sits just below the tongue.
The parotid gland contains mainly serous cells (secrete protein in watery fluid which contribute to saliva). It receives parasympathetic secretomotor innervation. Pregangalionic parasympathetic fibres of the glossopharyngeal nerve constitute the lesser petrosal nerve which projects to the otic ganglion. From here, postganglionic fibres project to the parotid gland via ‘hitchhiking’ with the auriculotemporal nerve, a branch of mandibular division of the trigeminal (CNV3).
The submandibular gland contains a mixture of serous and mucous cells. The sublingual gland contains mostly mucous cells. For both, preganglionic parasympathetic fibres originate from the chorda tympani of the facial nerve, but ‘hitchhike’ with the lingual nerve, a different branch of CNV3, to the submandibular ganglion. From here, postganglionic parasympathetic fibres can either project directly to the sublingual and submandibular glands, or can jump back into the lingual nerve and project as part of it.
Describe the central pathways for taste.
Once taste information is received from the tongue (both anterior and posterior), it travels to the gustatory nuclei of the medulla, and subsequently to the ventral posteromedial (VPM) nucleus of the thalamus. From here, pathways project to the primary gustatory cortex, encompassing the anterior insula and the frontal operculum.
Describe what is known about the higher processing of pain.
It was originally believed that the cortex had little or no role in pain perception, however, modern imaging studies have revealed that the cortex is activated following noxious stimuli. The areas activated include the primary and secondary somatosensory cortices in the parietal lobe, as well as the anterior cingulate cortex and insular cortex. The somatosensory cortices are thought to interpret the discriminative aspects of noxious stimuli (e.g. location, duration, nature of stimulus, intensity). The anterior cingulate and insular cortices are thought to interpret the affective and motivational aspects (unpleasantness from cingulate and emotional response (distress) from insular). Evidence for these comes mostly from lesion studies.
Briefly explain how pain can be mediated by descending pathways.
Electrical stimulation of the brainstem (especially near the periaqueductal grey matter) has been found to cause very effective analgesia in rats. This is known as stimulation-produced analgesia (SPA), and has been demonstrated in humans. This phenomenon is poorly understood, but it is thought to involve neurons in the raphe nuclei of the medulla which release 5-HT in the spinal cord. Opiate drugs administered to the periaqueductal grey matter, raphe, or spinal cord, also facilitate pain relief.
Explain some of the key issues with the traditional pain pathway.
Severe injuries don’t always cause pain- this was documented in WW2 where ~30% of soldier with severe injuries did not report any pain. This was proposed to be due to their high stress levels, however, it was later noted that 28% of civilians who sustained severe injuries from unanticipated incidents also did not report any pain. The reason for this remains unknown.
Another problem with our current understanding is that pain can occur without any obvious injury or disease. Pain is heavily affected by psychological factors- placebos are very effective for treating pain. This strong placebo response has been recognised to thwart development of painkilling drugs (since it is hard to prove the drug is an effective painkiller if the placebo cohort also reports loss of pain).
Acupuncture can reduce pain- nobody knows why.
Severing the “pain pathway” by anterolateral cordotomy (cauterising the spinothalamic tract) does not always reduce pain permanently- it is initially effective but can return, the mechanism for this is not understood.
Explain the theory and applications of gate theory.
It has been widely observed that rubbing the skin near an injury can suppress pain. It is proposed that this is due to inhibitory interneurons branching in the spinal dorsal horn, projecting from low threshold mechanoreceptors onto 2nd order spinothalamic neurons. This is known as the gate theory. This has been used to develop transcutaneous electrical nerve stimulation (TENS), a treatment for pain which uses stimulation of low threshold mechanoreceptive afferents to reduce pain. These larger diameter fibres are more easily excitable than the finer nociceptor fibres, so will become activated at weaker electrical stimuli. This treatment has been found to be effective in some cases but not always. Epidural spinal cord stimulation can also be used to suppress chronic pain, and this is thought to work also through inhibitory low threshold interneurons.
Describe the sensory innervation of skeletal muscle.
About 2/3 of all muscle fibres are sensory (twice as many as motor). Muscle activation and coordinated muscle control depends centrally on the sensory innervation, and good control of movement absolutely requires good sensory information. Your capacity to conduct fine motor tasks is sharply reduced when sensory input is lost (for example, when your hands are cold it is difficult to do your buttons; anaesthesia from the dentist slurs speech). There are three main sensory endings which produce large diameter, myelinated afferent fibres- muscle spindles (Ia and II) and Golgi tendon organs (Ib):
Muscle spindles are large, complex mechanoreceptors. They are fast conducting modified muscle fibres. They give rise to two types of sensory ending- primary (Ia), which are sensitive and respond to stretch and acceleration (rate of change of length) and secondary (II) which respond to absolute length of muscle. The sensitivity of both these endings can be adjusted by an independent motor system- gamma motoneurons, which sit in parallel with alpha motoneurons (the ones which innervate extrafusal fibres to deliver force), regulate the information flow of these afferents to the CNS.
Golgi tendon organs are large mechanoreceptors inserted in connective tissue fascicles which make up the tendon. They give rise to large diameter sensory fibres (Ib), and are very sensitive to active force development (respond to force exerted rather than stretch).
Describe the sensory innervation of joints.
Joint receptors are found within connective tissues which comprise joint capsules and ligaments, and are also associated with fat pads. These are similar in structure to Golgi, Ruffini, and Pacinian corpuscles (skin primary afferents). The are free nerve endings which respond to forces in connective tissue, and there are rapidly and slowly adapting types. They have group II, III, and IV afferents.
What are the differences between group I, II, III, and IV sensory afferent fibres?
Group I sensory afferents detect proprioception from skeletal muscle. They are large diameter, melinated axons.
Group II sensory afferents are almost all LTMs in skin. They are still large (but slightly smaller) diameter, myelinated axons.
Group III sensory afferents detect pain and temperature, and are fine, myelinated axons.
Group IV detect pain, temperature, and itch, and are very fine, unmyelinated axons.
What is proprioception and how can it be conveyed?
Proprioception refers to the signals that help the nervous system control movement and posture, both at conscious and subconscious levels. This allows us to know the position of our body parts with respect to each other and with respect to the 3D space around us. This can be divided into stataesthesis and kinaesthesis- awareness of the relative positions of our body parts in space, and awareness of movement of our joints (speed and direction), respectively.
There are two possible ways by which movement and position could be reported to the brain- corollary discharges, and sensory feedback. Corollary discharges are copies of motor commands within the brain. Essentially, when the brain initiates a descending movement command to skeletal muscle, it may branch into a corollary discharge which feeds this information back to another brain area to inform it of the movement. Sensory feedback could come from signals from proprioceptors within the muscle, skin, joints, etc. The corollary discharge method is most important in assessing, for instance, the heaviness of an object. Here, specific motor commands are important for judging information. Sensory feedback is most important when it comes to evaluating the position of the body in space.
Explain how flexion/extension of a joint is detected by muscle spindles.
Flexion/extension of a joint is detected by muscle spindles, where receptors within opposite muscles detect stretch. They therefore provide complementary information about flexion and extension of joints by relaying opposing information about the contraction (length) of the muscle fibres themselves.
To use the elbow as an example, this information can come from the biceps and the triceps. When the elbow is flexed, the bicep muscle is contracted, and is therefore shorter, reducing the firing rate of muscle spindles in the bicep; whereas the tricep is relaxed, increasing the firing rate of its muscle spindles.
Describe the sensory and motor nerve supply of the larynx.
Sensation just above the vocal folds is supplied by the internal branch of the superior laryngeal nerve; sensation below the vocal folds is supplied by the recurrent laryngeal nerve (branch of vagus, CNX)
All intrinsic muscles of the larynx are supplied by the recurrent laryngeal nerve. There is one exception to this- the cricothyroid is supplied by the external branch of the superior laryngeal nerve (also branch of CNX). The vagus nerve descends alongside the trachea bilaterally. The right recurrent laryngeal nerve branches off the right vagus as it passes the right subclavian artery, and then wraps around the artery and ascends back up to innervate the muscles of the larynx. The left recurrent laryngeal nerve branches into the recurrent which loops around the aorta before ascending (not symmetrical).
Describe the mechanism of anaelgesic action of opioid drugs.
Opioid receptors activate Gi/Go proteins to inhibit adenylate cyclase, reducing intracellular cAMP (agonists at opioids receptors- inhibitory GPCRs). They also activate potassium channels, inhibit calcium channels, and activate the MAPK (mitogen-activated protein kinase) cascade. They therefore have the overall effect of reducing neuronal excitability, and therefore decrease neuronal activity. However, they can also increase neuronal activity by disinhibition of inhibitory interneurons (inhibition of inhibitory cell will increase excitation of subsequent cell).
There are three main opioid receptors classes, as well as an opioid-like receptor class. Mu receptors are expressed for endogenous endorphins, and are the main site of opioid analgesics (utilised by most synthetic opioids). Delta receptors are for enkephalins, and Kappa receptors are for dynorphins. All are expressed throughout the brain and spinal cord, as well as peripheral nerve endings. These receptors rarely operate in isolation, but form complexes with other GPCRs (don’t understand the significance of this yet).
Analgesic effect of opioids is mediated in the periphery, spinal cord, and brain- however, this is predominantly attributed to inhibition of nociceptive afferents within the spinal cord dorsal horn. They are especially effective at treating inflammatory pain. They also inhibit spinal reflexes and transmission of nociceptive impulses through the dorsal horn (both post- and pre-synaptic effects), can cause localised release of endorphins in the brain and spinal cord, and may induce release of 5-HT from the raphe nucleus (would contribute to analgesic effects). Although all opioids exhibit analgesics properties, not all elicit the same broad spectrum of pharmacological effects which is seen in morphine.
Explain the effects of opioid drugs on the CNS.
Opioids are also known to reduce the affective (perceptive) component of pain, reflecting effects on the limbic system (certain opioids such as pentazocine, do not have this effect). The analgesic effects of opioids is mostly mediated via mu receptors (but there is also some evidence of delta and kappa activation). Prolonged opioids use can cause paradoxical hyperalgesia- this is increased sensitivity to pain, but is not associated with tolerance (i.e. not due to sensitisation). It is more likely due to alterations in neural network structures within the CNS.
The feeling of euphoria may also contribute to analgesic effects of opioids, and reduces agitation and anxiety associated with illness of injury. IV administration of these drugs causes a spike in blood concentrations which is not seen from oral administration, meaning that the euphoric effect is much more pronounced. Euphoria is also mostly mediated by mu receptors. Kappa receptors elicit the opposite effect (cause dysphoria and hallucinations), but most opioid drugs have a greater affinity for mu.
Respiratory depression is a major adverse side effect of opioid drugs, including morphine- it is the leading cause of death in addicts. Opioids depress breathing via their effects on mu receptors in the pre-Botzinger complex (a respiratory rhythm generating area of the medulla). It also suppresses the hypercapnic reflex (increased ventilation due to elevated PCO2), preventing rectification. However, opioids do not suppress cardiovascular function.
Other CNS-mediated side effects of opioid use include depression of the cough reflex, nausea and vomiting, and pupillary constriction. The mechanisms underlying cough reflex depression is poorly understood, but they do not correlate with the analgesic effects (some opioids are used as cough medicines). Nausea and vomiting is mediated by the area postrema on the floor of the 4th ventricle- the BBB is particularly weak at this site, and lots of opioid receptors are expressed here, leading to increased chances of vomiting in most patients. Pupillary constriction is caused by activation of mu and kappa receptors in the oculomotor nucleus- it is useful in diagnosis as tolerance to this effect is not acquired.
