Lesions of the peripheral or central nervous pathways for pain typically result in a loss or impairment of pain sensation. Paradoxically, damage to or dysfunction of these pathways can produce pain. For example, damage to peripheral nerves, as occurs in diabetic neuropathy, or to primary afferents, as in herpes zoster, can result in pain that is referred to the body region innervated by the damaged nerves. Though rare, pain may also be produced by damage to the central nervous system, particularly the spinothalamic pathway or thalamus. Such neuropathic pains are often severe and are notoriously intractable to standard treatments for pain. Neuropathic pains typically have an unusual burning, tingling, or electric shock-like quality and may be triggered by very light touch.
These features are rare in other types of pain. On examination, a sensory deficit is characteristically present in the area of the patient’s pain. Hyperpathia is also characteristic of neuropathic pain; patients often complain that the very lightest moving stimuli evoke exquisite pain (allodynia). In this regard it is of clinical interest that a topical preparation of 5% lidocaine in patch form is effective for patients with postherpetic neuralgia who have prominent allodynia. A variety of mechanisms contribute to neuropathic pain.
As with sensitized primary afferent nociceptors, damaged primary afferents, including nociceptors, become highly sensitive to mechanical stimulation and begin to generate impulses in the absence of stimulation. There is evidence that this increased sensitivity and spontaneous activity is due to an increased concentration of sodium channels. Damaged primary afferents may also develop sensitivity to norepinephrine. Interestingly, spinal cord pain-transmission neurons cut off from their normal input may also become spontaneously active. Thus, both central and peripheral nervous system hyperactivity contribute to neuropathic pain.
Sympathetically Maintained Pain. Patients with peripheral nerve injury can develop a severe burning pain (causalgia) in the region innervated by the nerve. The pain typically begins after a delay of hours to days or even weeks. The pain is accompanied by swelling of the extremity, periarticular osteoporosis, and arthritic changes in the distal joints. The pain is dramatically and immediately relieved by blocking the sympathetic innervation of the affected extremity. Damaged primary afferent nociceptors acquire adrenergic sensitivity and can be activated by stimulation of the sympathetic outflow. A similar syndrome called reflex sympathetic dystrophy can be produced without obvious nerve damage by a variety of injuries, including fractures of bone, soft tissue trauma, myocardial infarction, and stroke. Although the pathophysiology of this condition is poorly understood, the pain and the signs of inflammation are rapidly relieved by blocking the sympathetic nervous system. This implies that sympathetic activity can activate undamaged nociceptors when inflammation is present. Signs of sympathetic hyperactivity should be sought in patients with posttraumatic pain and inflammation and no other obvious explanation.