Key Topics

• • Pathophysiology of pain
• • Pain management medications
  • Local anaesthesia
  • General anaesthesia and sedation
  • Analgesics
  • Chronic pain medications

Learning Objectives

• • To be able to identify the key neurological components of the pain pathway
• • To be able to identify the mechanism of action of local anaesthesia
• • To be able to identify the key medications used in general anaesthesia and sedation
• • To be able to list the key analgesics
• • To be able to list the main adjuvant chronic pain medications

Introduction

In answer to the question, ‘what is pain?’ probably the most widely used definition is that provided by the International Association for the Study of Pain (IASP), which describes pain as, ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’.

In terms of a modern understanding the nature of pain and how it is experienced, in 1968 Ronald Melzack and Kenneth Casey described the ‘3 dimensions of pain’ – in so far as pain comprises three interactive domains: ‘sensory-discriminative’ (intensity, character, location, and duration of the pain); ‘affective-motivational’ (unpleasantness and urge to escape the unpleasantness of the pain) and ‘cognitive-evaluative’ (interplay of cognitions such as prior experiences, appraisal, cultural values and distraction). This was an important watershed in the understanding of pain, as it suggested that the intensity (sensory-discriminative) and unpleasantness (affective-motivational) aspects of pain were not just determined by the magnitude of the painful stimulus, but were also influenced by an individual’s intrinsic cognitive functions.

The experience of pain is very subjective and is influenced by many factors such as gender, mood, cultural beliefs, distraction, catastrophizing (negative thinking about the pain experience), and genetics. The physiological processing of pain is a complex interaction between the central and peripheral nervous systems (Figure 8.1)

Nociceptors

The nociceptors are the sensory receptors that detect noxious stimuli, converting these into electrical impulses which are conducted into the central nervous system (CNS) via the Aδ and C fibres. These primary afferent (conducting towards the CNS) Aδ and C fibres are distributed throughout the body (skin, viscera, muscles, joints, meninges), and can be triggered by mechanical, thermal or chemical stimuli. Inflammatory mediators such as prostaglandins, bradykinin, cytokines and serotonin are released from damaged tissues and can directly stimulate nociceptors. Moreover, such mediators can sensitize tissues by reducing the threshold at which nociceptors are activated (the amount of stimulation required to produce a pain signal is reduced) – a process known as ‘primary sensitization’.

Dorsal horn of the spinal cord

The Aδ and C primary afferent neurones synapse with secondary afferent neurones in the dorsal horn of the spinal cord. The Aδ and C terminals release a number of excitatory neurotransmitters including substance P and glutamate. Secondary afferent neurones then transmit the signals to the brainstem and brain via the spinothalamic and spinoreticular tracts. The third-order afferent neurones located within the thalamus transmit the pain signals to the higher centres of the brain within the cortex.

In addition to afferent pain signals travelling to the higher pain centres in the brain, inhibitory pain modulation arises in certain areas of the brain (e.g. periaqueductal grey matter), which are highly concentrated with opioid receptors (one reason why opioid drugs are effective analgesics). These inhibitory centres project down to the dorsal horn and inhibit pain signals – the pathways being monoaminergic, with noradrenaline and serotonin acting as neurotransmitters.

While the somatosensory cortex plays an important role in the localization of pain, functional magnetic resonance imaging has identified up to 11 areas of the brain that are thought to be involved in the acute pain experience. This collective is commonly known as the ‘pain matrix’, and includes the somatosensory cortex, insula, anterior cingulate cortex and thalamus.

Acute and chronic pain

There is debate about when a painful condition is deemed to be acute or chronic. Classically, the arbitrary cut off for acute pain was 3 months duration; however, some suggest that chronic pain can be simply defined as ‘pain that extends beyond the expected period of healing’. Within chronic pain conditions, the pain no longer serves its useful protective purpose – acute pain highlights injury or disease, while chronic pain persists, despite the original injury healing.

Neuropathic pains

Neuropathic pains are defined by IASP as, ‘pain arising as a direct consequence of a lesion or disease affecting the somatosensory system’. Neuropathic pains are more often chronic in nature and usually present with continuous or persistent pain symptoms; they are often experienced in response to a stimulus that does not usually cause pain (allodynia), or may produce a heightened response to a stimulus that is normally painful (hyperalgesia).

Chronic orofacial pain conditions:

Persistent pains are not uncommon in the mouth and face, and can occur in the absence of any relevant pathology following around 5% of surgical endodontics, or between 3–15% of orthograde root canal treatments. Examples of orofacial pain conditions that are considered to be neuropathic in origin are – burning mouth syndrome (BMS), persistent idiopathic facial pain, trigeminal neuropathic pain and trigeminal neuralgia. Pain-related temporomandibular disorder (TMD) is not thought to be a neuropathic condition and is reported to affect around one-third of the population at some point in their lives.

Role of pain medications within pain management

The World Health Organization (WHO) has promulgated the ‘analgesic ladder’ as guidance for pain prescribing (Figure 8.2). Initially the ladder was devised for cancer-related analgesia but has since been adopted for all types of pain. The general principle is to start with simple analgesics and depending on response escalate to stronger treatments. When looking at the analgesic ladder, ‘non-opioid’ analgesics would be medications such as paracetamol and ibuprofen; ‘opioid for mild to moderate pain’ would be the likes of codeine; ‘opioids for moderate to severe pain’ would be treatments such as morphine and diamorphine; ‘adjuvant’ treatments relates to medications such as amitriptyline and gabapentin. When applying the WHO analgesic ladder to oral and facial pain prescribing, opioids are rarely indicated outside the management of acute pain (e.g. post-operative pain control) or palliative care (e.g. terminal cancer). Prescribing opioids for chronic facial pain conditions (e.g. TMD or BMS) is not recommended – they have limited if any evidence to support efficacy and if prescribed for long courses can cause significant issues with dependency and side-effects.

It is important to remember that it may not be possible to provide any treatments that will completely remove all chronic pain symptoms; rather the emphasis should be more upon pain management. Medications only form one part of chronic pain management – which also includes areas such as: patient education, physical exercises/relaxation techniques, physiotherapy and clinical psychology. The overall aim for chronic pain management is to promote self-management of the patient’s condition, and to improve quality of life in spite of the pain continuing to be present.

Local anaesthesia

Local anaesthetics are membrane stabilizing agents; which act mainly by inhibiting sodium influx through the sodium channels in the neuronal-cell membranes. The inhibition of sodium influx results in the nerve action potential not occurring, and signal conduction being prevented (Figure 8.3). Local anaesthetic agents bind more readily to sodium channels in activated, excitable membranes, such as those associated with the nociceptive fibres.

Local anaesthetic agents are split into ‘amide’ and ‘ester’ types – determined by their molecular structure. The majority of local anaesthetics currently used in dentistry are amide-type agents (e.g. lidocaine, articaine, prilocaine) compared to a relative few ester-type drugs (e.g. procaine, benzocaine, cocaine) – due in part to an increased level of allergic reactions noted in the older ester-type agents.

Local anaesthetics are weakly alkaline bases which usually exist as hydrochloride salts, thus allowing them to exist in an aqueous solution. Therefore, local anaesthetics are either in a protonated (ionized), or unprotonated (unionized) form – with only the unprotonated form readily diffusing across cell membranes. Once the unprotonated base enters the cell, it ionizes to the active protonated form, which in turn binds to the sodium channels. The protonated form of the drug does not readily pass through the cell membrane, thus trapping it within the cell (Figure 8.3).

Acidotic tissues, such as those associated with inflammation and infection can partly negate the effect of local anaesthetics – due to the ionization of the local anaesthetic base within the tissues – thus reducing the amount of unionized anaesthetic that can penetrate the nerve-cell membrane.

Although all nerve fibres can be affected by local anaesthetics, on account of differences in nerve diameter and myelination, there are differing sensitivities to local anaesthetic blockade. Type B fibres (sympathetic nerves) are the most sensitive, followed by C fibres (pain), Aδ (temperature), Aγ (proprioception), Aβ (touch and pressure), with the least sensitive being Aα (motor). This ‘differential blockade’ explains why dental anaesthesia removes the sensation of pain, but often doesn’t prevent the experience of pressure or movement.

Local anaesthetic agents used in dentistry vary in their potencies, and as a result exist in solutions for injection of variable concentration (Table 8.1