**3. Pathophysiology**

and

nerve root

and T<sup>1</sup>

due to iatrogenia [8–16], particularly during lymph node biopsy [17, 18] or treatment of some

The *pain* is chronic [20], persistent [7], constant [21], burning [22] and throbbing [17], with par-

The *pain is distributed* in the distal areas of the upper limb, covering several dermatomes, mostly the caudal ones [24] and particularly the hand [5, 17, 23, 25]. The paroxysmal pain is felt in the arm [26]. Allodynia, hypersensitivity and electric-like discharges are present at the border between the normal and affected dermatomes [17, 26–29], particularly between T<sup>1</sup>

The *pain severity* correlates with the magnitude of the brachial plexus injury [2, 3] and to the number of avulsed nerve roots [2–4, 21, 26, 30–33], particularly when the lower roots are

The *pain* does not *appear* immediately after the injury but a few days later [24] and no longer

The *neuropathic pain can be associated with* phantom [37] or stump pain [38] in case of upper limb amputation, or to complex regional pain syndrome (CRPS) [6], inducing a complex pain

*Self-mutilation* has been described in 5–29% of obstetric brachial plexus injury cases [39, 40].

The *quality of life* is seriously impaired with sleep disorders, family troubles, unemployment, chronic depression and social withdrawal [2, 5, 6, 17, 21, 41–44]. Additionally, the chronic pain is a further hindrance to comply with a good rehabilitation programme, impairing a possible functional recovery [6, 45, 46]. Among all the disabilities induced by the brachial plexus injury, the pain has been found to be the symptom that most negatively affects the quality of life [47]. *Treatment* of this chronic pain can be troublesome, as the response to the different treatment modalities is poor and not all of them allow preservation of the remaining upper limb function [2, 5, 48].

Although 50–82.7% of brachial plexus injuries suffer from chronic pain [2, 3, 5, 6, 17, 35, 49–51], it is severe in 41% of them [32]. The incidence and severity are higher in nerve root avulsions [2–4, 7, 21, 30, 33], especially when all the roots are avulsed [2, 17, 21]. Overtime there is a spontaneous progressive improvement, so just after the injury 90% of patients suffer

*Predisposing factors*: the strongest is alcohol abuse [17], but smoking [6, 17], other coexistent pain conditions [6], like psychiatric co-morbidities [6, 17], using a sling [5] and the marital status (both married or divorced versus being single) also increase the pain incidence [5]. A longer time using a sling increases the chance of chronic pain because limb movement restric-

from pain but affects only 30% of them 3 years later [35, 36, 49].

tion has a negative impact on recovery [5].

oxysmal discharges [3, 6, 23], particularly upon gentle rubbing the affected area [4].

affected [24, 34, 35]. Nevertheless, Bertelli et al. [21] found that in isolated C8

malignancies [19].

104 Treatment of Brachial Plexus Injuries

at the posterior aspect of the elbow [26].

avulsions, there was no pain at all.

than 3 months after it [5, 6, 24, 26, 35, 36].

condition rather difficult to control [19, 30, 31].

T2

**2. Incidence**

The neuropathic pain is induced by an injury to the somatosensory pathways [56, 57] like a brachial plexus injury, an upper limb amputation or both of them simultaneously [2, 7, 58].

The peripheral nerve injury induces deafferentation [2] and damage to the C nerve fibres [59]. The dorsal horn neurons devoid of their peripheral sensorial input start to fire spontaneously and erratically [60–64], stimulating pain sensation in the higher central nervous system levels [65, 66]. In experimental studies it has been found that the spinal cord microglia and astrocytes are activated at the injury site [67] and help to maintain the neuropathic pain [68–72]. Higher levels like the thalamus and the motor cortex also undergo the same process by which deafferented neurons create new synapses and reorganize and start firing in abnormal patterns [7, 73–77]. Descending pathways modulate the neuropathic pain [78] creating new circuits that induce and maintain it [79–81]. The brain and spinal cord neuronal reorganization leads to an increased sensitivity to otherwise normal stimuli, lowering the threshold required to feel the sensation as pain and inducing secondary hyperalgesia and allodynia [4, 82]. It also explains why the pain often extends beyond the denervated area [26, 33] and why it manifests at the border areas between the partially denervated and normal dermatomes [17, 27].

As mentioned above the pain seen after brachial plexus injury has two distinct patterns: paroxysmal and continuous. The first one is thought to originate from the deafferented posterior spinal horn neurons [60, 83], while the second one comes from the thalamus [74, 84]. In the phantom limb pain, the brain cortex undergoes a functional reorganization in response to the chronic pain [40, 85, 86].

Some have suggested that the neuropathic pain after brachial plexus avulsion is generated not by the avulsed nerve roots but by the remaining ones [67] that are also injured, although not so severely [34]. Although this might be true in some cases, it does not explain why the neuropathic pain severity is maximal when all nerve roots are avulsed [2, 17, 21, 55].
