The basic science oral
Basic science oral core topics

• Embryology
  
  Limb embryology
  At 3 weeks in utero (wiu)
  Gastrulation occurs, i.e. the formation of ectodermal and endodermal plates. The primitive streak forms, and mesenchymal tissue gives rise to mesoderm. The notochord is formed of ectodermal tissue. Neurulation occurs, i.e. the ectodermal neural plate forms a neural crest and tube. Somatization occurs,
  i.e. mesoderm gives rise to 42–44 pairs of somites, each with a dermatome, myotome and sclerotome.
  
  At 4 wiu
  Folding of embryo into “C shape”. The apical ectodermal ridge (AER) forms. Limb buds appear – mesoderm covered by a thin surface of ectoderm.
  
  At 7 weeks onwards
  Rays and then digits form under the control of the zone of polarizing activity (ZPA). Mesenchymal condensations form cartilage anlage (models), which will become primary centres of ossification.
  The limb buds develop between 4 and 6 weeks and quickly form the upper extremities with pro-nated forearms that then rotate externally. A few days later the lower extremities form and rotate internally. Vascular buds invade the cartilage model bringing in osteoprogenitor cells, which differentiate into osteoblasts and form primary centres of ossification at 8 weeks. Although finger rays are present at 7 weeks the hands continue to differentiate until 13 weeks.
  
  Control of limb development Apical ectodermal ridge (AER)
  The AER is a thickening of the distal ectoderm covering the limb bud which influences the underlying mesoderm to promote and control growth. The AER directs the growth of the limb bud in a proxi-modistal (PD) direction. The AER releases chemical signals, particularly fibroblast growth factor (FGF). Experimental removal of the AER or loss of contact of the AER with limb bud mesoderm prevents limb development.
  
  Zone of polarizing activity (ZPA)
  The ZPA is a zone of tissue at the posterior aspect of the limb bud. It is important in specifying the number of digits along the AP axis. This activity is mediated by the gene SHH (sonic hedgehog). SHH activates a group of homeobox genes, which specify the number of digits.
  
  Growth factors
  Growth factors are important in signalling along the dorsoventral (DV) axis.
  
  Spine embryology

• Vertebrae are each formed of two adjacent scle-rotomes from the third week onwards
• There are two centres of ossification, one from each sclerotome, which fuse to form a single centrum
• Notochord persists as the nucleus pulposus of the
  intervertebral disc

• The neural arch also forms two centres, which do not fuse together until the postnatal period, and to the centrum at around 5 years of age
  
  Pain
  Management
  Management broadly follows the pain ladder. An acute pain team service should be viewed as an adjunct to pain management and should be involved early where significant pain control issues
  are anticipated (e.g. amputees).
  Physiology
   

• Ad fibres. Myelinated. Sharp, acute pain
• C fibres. Unmyelinated (slow to conduct). Dull
  ache, prolonged pain
  
  Pathways
• Via dorsal spinal roots
• C fibres to substantia gelatinosa (layers II and III
  of grey matter)
• A fibres to layers I and V of grey matter
• Second-order ascending fibres pass contralater-ally via the dorsal/posterior column or spinotha-lamic tract

Sympathetic – may increase blood flow (and
therefore pain) in a limb

Gate theory
Afferent impulses to the substantia gelatinosa are modulated there. Descending neurones from the brain are thought to act as a “gatekeeper” to determine the extent of secondary neuronal activation.

Endorphins
Endorphins are endogenous opiates acting as inhibitors of the pain pathway. They act on d, k and µ receptors.

Acute pain management
Diagnosis
Ascertaining the cause of pain should take equal priority with efforts to reduce pain, since diagnosis may lead to a specific pain-reducing intervention (e.g. compartment syndrome will not be relieved by anything short of surgery, fractures require adequate splintage, etc.).
Pain ladder
Originally devised by the World Health Organization for cancer relief but more widely applied to pain of other aetiologies and chronicities. There are three main classes:
Non-opioid – paracetamol, aspirin (and other NSAIDs)
Weak opioid – codeine, dextropropoxyphene, co-codamol, etc.
Strong opioids – morphine, diamorphine
Where optimal use of a drug in one class does not give adequate analgesia, move up a level. Co-analgesics may be added to any step in the ladder.

Chronic pain management
A multidisciplinary team-based approach is favoured. Dedicated chronic pain clinics are appropriate for intractable pain:
Diagnosis – must be thorough to rule out causes where specific management may be curative (e.g. missed spinal stenosis).
Psychology – chronic pain of benign aetiology is frequently associated with clinical depression, whereas chronic pain of neoplastic aetiology is seldom associated with depression. Lifestyle change and antidepressants have a role.
Analgesia – the analgesic ladder should be applied (see above). Aim for regular medication with the option of extra doses for “breakthrough pain”. Oral medication is favoured.
Co-analgesics – are drugs used in conjunction with traditional analgesic agents:
NSAIDs – good for bone pain (but have negative effect on bone and soft tissue healing!)
Tricyclic antidepressants – good for nerve damage pain.
Calcium channel blockers (nifedipine) – good for sympathetic mediated pain (e.g. Raynaud’s).
Steroids – can relieve pain in inflammatory arthropathy.
Muscle relaxants – may have a role where spasticity is a problem (cord injury).
Stimulation – acupuncture, ice, heat, ultrasound, TENS are all thought to act via a gating effect on myelinated fibres.
Nerve blocks – temporary via local anaesthetic, permanent with phenol or radiofrequency ablation. Examples – epidural or peripheral plexus blocks.
Neurosurgery – has a limited role, e.g. rhizotomy, ablation of PIN at wrist.